Macrophage

Where it participates (unsigned role)

1. The carbohydrate polymers known as beta-1,3-D-glucans exert potent effects on the immune system, stimulating antitumour and antimicrobial activity for example, by binding to receptors on macrophages and other white blood cells and activating them, and although beta-glucans are known to bind to receptors such as complement receptor 3 there is evidence that another beta-glucan receptor is present on macrophages, which is identified here as dectin-1.

   Dectin-1 / CLEC7A → Beta-glucan source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/glucan-research/11544516.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14e7f5285cdda3bdcf3596e5e9517683d195dd4a4ae42ff1f9d07f1d3288bf1c", "start_char": 0, "end_char": 573, "text_sha256": "14e7f5285cdda3bdcf3596e5e9517683d195dd4a4ae42ff1f9d07f1d3288bf1c"}

   experimental_model

   Identification of the unknown macrophage beta-glucan receptor

   exposure

   Beta-1,3-D-glucans binding to macrophage surface receptors

   limitations

   A brief communication announcing the identification. It states that beta-glucans were already known to bind complement receptor 3, so it adds a receptor rather than replacing one.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Mouse and human cells

   plain_language

   A second receptor for these sugars was identified, alongside the complement receptor already known to bind them.

   primary_references

   [bg-p11544516] Immune recognition. A new receptor for beta-glucans. (2001). https://pubmed.ncbi.nlm.nih.gov/11544516/ DOI: 10.1038/35092620

   tissue_or_cell_type

   Macrophage

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 99–110

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Identification of the unknown macrophage beta-glucan receptor · source_derived_draft · unverified_draft

   ### bg-dectin1-is-the-unknown-receptor The carbohydrate polymers known as beta-1,3-D-glucans exert potent effects on the immune system, stimulating antitumour and antimicrobial activity for example, by binding to receptors on macrophages and other white blood cells and activating them, and although beta-glucans are known to bind to receptors such as complement receptor 3 there is evidence that another beta-glucan receptor is present on macrophages, which is identified here as dectin-1. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: A second receptor for these sugars was identified, alongside the complement receptor already known to bind them. organism: Mouse and human cells tissue_or_cell_type: Macrophage experimental_model: Identification of the unknown macrophage beta-glucan receptor limitations: A brief communication announcing the identification. It states that beta-glucans were already known to bind complement receptor 3, so it adds a receptor rather than replacing one. exposure: Beta-1,3-D-glucans binding to macrophage surface receptors evidence_span: {"source_cache": "artifacts/glucan-research/11544516.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14e7f5285cdda3bdcf3596e5e9517683d195dd4a4ae42ff1f9d07f1d3288bf1c", "start_char": 0, "end_char": 573, "text_sha256": "14e7f5285cdda3bdcf3596e5e9517683d195dd4a4ae42ff1f9d07f1d3288bf1c"} [bg-p11544516] Immune recognition. A new receptor for beta-glucans. (2001). https://pubmed.ncbi.nlm.nih.gov/11544516/ DOI: 10.1038/35092620

   Complete structured claim and evidence

2. Non-opsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody against CR3, demonstrating that CR3 was not the beta-glucan receptor mediating this activity, and using the novel anti-Dectin-1 antibody 2A11 Dectin-1 was shown to be almost exclusively responsible for the beta-glucan-dependent non-opsonic recognition of zymosan by primary macrophages, defining Dectin-1 as the leukocyte beta-glucan receptor first described over 50 years ago and resolving the long-standing controversy regarding the identity of this important molecule.

   Dectin-1 / CLEC7A → Non-opsonic recognition of a yeast particle source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/glucan-research/12163569.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "533d8630c3d727db58869724825f47c5241cf9c3159acce359d3bc8b0fdb2a6a", "start_char": 0, "end_char": 1365, "text_sha256": "533d8630c3d727db58869724825f47c5241cf9c3159acce359d3bc8b0fdb2a6a"}

   experimental_model

   Carbohydrate inhibition, CD11b-deficient cells and a new anti-Dectin-1 monoclonal antibody applied to non-opsonic zymosan binding

   exposure

   Zymosan binding to primary macrophages with specific carbohydrate inhibitors, CD11b deficiency, a blocking anti-CR3 antibody and the novel anti-Dectin-1 antibody 2A11

   limitations

   The ligand is zymosan, which is a mannan-rich particle as well as a glucan one, and the readout is non-opsonic binding rather than every glucan response.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Mouse

   plain_language

   Removing the complement receptor entirely did not change how macrophages grabbed yeast particles; blocking the other receptor did.

   primary_references

   [bg-p12163569] Dectin-1 is a major beta-glucan receptor on macrophages. (2002). https://pubmed.ncbi.nlm.nih.gov/12163569/ DOI: 10.1084/jem.20020470

   tissue_or_cell_type

   Primary macrophage

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 112–123

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Carbohydrate inhibition, CD11b-deficient cells and a new anti-Dectin-1 monoclonal antibody applied to non-opsonic zymosan binding · source_derived_draft · unverified_draft

   ### bg-dectin1-not-cr3-binds-zymosan Non-opsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody against CR3, demonstrating that CR3 was not the beta-glucan receptor mediating this activity, and using the novel anti-Dectin-1 antibody 2A11 Dectin-1 was shown to be almost exclusively responsible for the beta-glucan-dependent non-opsonic recognition of zymosan by primary macrophages, defining Dectin-1 as the leukocyte beta-glucan receptor first described over 50 years ago and resolving the long-standing controversy regarding the identity of this important molecule. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: Removing the complement receptor entirely did not change how macrophages grabbed yeast particles; blocking the other receptor did. organism: Mouse tissue_or_cell_type: Primary macrophage experimental_model: Carbohydrate inhibition, CD11b-deficient cells and a new anti-Dectin-1 monoclonal antibody applied to non-opsonic zymosan binding limitations: The ligand is zymosan, which is a mannan-rich particle as well as a glucan one, and the readout is non-opsonic binding rather than every glucan response. exposure: Zymosan binding to primary macrophages with specific carbohydrate inhibitors, CD11b deficiency, a blocking anti-CR3 antibody and the novel anti-Dectin-1 antibody 2A11 evidence_span: {"source_cache": "artifacts/glucan-research/12163569.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "533d8630c3d727db58869724825f47c5241cf9c3159acce359d3bc8b0fdb2a6a", "start_char": 0, "end_char": 1365, "text_sha256": "533d8630c3d727db58869724825f47c5241cf9c3159acce359d3bc8b0fdb2a6a"} [bg-p12163569] Dectin-1 is a major beta-glucan receptor on macrophages. (2002). https://pubmed.ncbi.nlm.nih.gov/12163569/ DOI: 10.1084/jem.20020470

   Complete structured claim and evidence

3. Barley and yeast beta-1,3-glucan were labelled with fluorescein to track their oral uptake and processing in vivo, orally administered beta-1,3-glucans were taken up by macrophages that transported them to spleen, lymph nodes and bone marrow, within the bone marrow the macrophages degraded the large beta-1,3-glucans into smaller soluble beta-1,3-glucan fragments that were taken up by the CR3 of marginated granulocytes, and these granulocytes with CR3-bound beta-1,3-glucan-fluorescein were shown to kill iC3b-opsonized tumour cells following their recruitment to a site of complement activation resembling a tumour coated with monoclonal antibody.

   Transport of ingested glucan by macrophages to spleen, lymph node and marrow → Beta-(1->3)-linked gluco-oligosaccharides source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/glucan-research/15240666.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eaff7297fa40df19ef82e5e1de433ec0cf34590a7e3fda6aa6061e0922666781", "start_char": 0, "end_char": 1454, "text_sha256": "eaff7297fa40df19ef82e5e1de433ec0cf34590a7e3fda6aa6061e0922666781"}

   experimental_model

   Fluorescein-labelled oral glucans tracked through macrophages to marrow, with therapy in C3-deficient and CR3-deficient mice

   exposure

   Orally administered barley beta-1,3;1,4-glucan and orally administered yeast beta-1,3;1,6-glucan, each with antitumour monoclonal antibody

   limitations

   The single experiment in this collection that tested a cereal mixed-linkage glucan and a yeast branched glucan side by side in the same protocol. It is a mouse tumour model, and oral uptake in mice does not establish the same uptake in people.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Mouse

   plain_language

   Swallowed glucan is carried to the marrow inside macrophages, cut up there, and handed to granulocytes on the way out.

   primary_references

   [bg-p15240666] Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. (2004). https://pubmed.ncbi.nlm.nih.gov/15240666/ DOI: 10.4049/jimmunol.173.2.797

   tissue_or_cell_type

   Gut, spleen, lymph node, bone marrow and tumour

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 255–266

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fluorescein-labelled oral glucans tracked through macrophages to marrow, with therapy in C3-deficient and CR3-deficient mice · source_derived_draft · unverified_draft

   ### bg-macrophages-carry-and-cut-it Barley and yeast beta-1,3-glucan were labelled with fluorescein to track their oral uptake and processing in vivo, orally administered beta-1,3-glucans were taken up by macrophages that transported them to spleen, lymph nodes and bone marrow, within the bone marrow the macrophages degraded the large beta-1,3-glucans into smaller soluble beta-1,3-glucan fragments that were taken up by the CR3 of marginated granulocytes, and these granulocytes with CR3-bound beta-1,3-glucan-fluorescein were shown to kill iC3b-opsonized tumour cells following their recruitment to a site of complement activation resembling a tumour coated with monoclonal antibody. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: Swallowed glucan is carried to the marrow inside macrophages, cut up there, and handed to granulocytes on the way out. organism: Mouse tissue_or_cell_type: Gut, spleen, lymph node, bone marrow and tumour experimental_model: Fluorescein-labelled oral glucans tracked through macrophages to marrow, with therapy in C3-deficient and CR3-deficient mice limitations: The single experiment in this collection that tested a cereal mixed-linkage glucan and a yeast branched glucan side by side in the same protocol. It is a mouse tumour model, and oral uptake in mice does not establish the same uptake in people. exposure: Orally administered barley beta-1,3;1,4-glucan and orally administered yeast beta-1,3;1,6-glucan, each with antitumour monoclonal antibody evidence_span: {"source_cache": "artifacts/glucan-research/15240666.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eaff7297fa40df19ef82e5e1de433ec0cf34590a7e3fda6aa6061e0922666781", "start_char": 0, "end_char": 1454, "text_sha256": "eaff7297fa40df19ef82e5e1de433ec0cf34590a7e3fda6aa6061e0922666781"} [bg-p15240666] Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. (2004). https://pubmed.ncbi.nlm.nih.gov/15240666/ DOI: 10.4049/jimmunol.173.2.797

   Complete structured claim and evidence

4. Dectin-1 activates Syk in macrophages and is important for Dectin-1-stimulated reactive oxygen production but not for phagocytosis, Syk activation is restricted to a subpopulation of macrophages that is in equilibrium with cells that cannot activate the pathway, and the proportion of macrophages using this signalling pathway can be modulated by cytokine treatment, so Dectin-1 signalling reveals dynamic macrophage heterogeneity in inflammatory activation potential.

   Dectin-1 / CLEC7A → Spleen tyrosine kinase / SYK source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/glucan-research/15956283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "05fbe0dae04d44d8af5946504f066c104e7a294b29d35d70463d50874ec7b41c", "start_char": 0, "end_char": 990, "text_sha256": "05fbe0dae04d44d8af5946504f066c104e7a294b29d35d70463d50874ec7b41c"}

   experimental_model

   Measurement of Syk activation and reactive oxygen production in macrophage subpopulations

   exposure

   Dectin-1 stimulation with assessment of Syk activation, reactive oxygen production and phagocytosis

   limitations

   The heterogeneity finding is the important limit: the pathway operated in a subpopulation in equilibrium with cells that could not use it, and the proportion shifted with cytokine treatment.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Mouse

   plain_language

   One kinase carries the oxidative burst but not the swallowing, and only some of the cells can run it at any moment.

   primary_references

   [bg-p15956283] Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. (2005). https://pubmed.ncbi.nlm.nih.gov/15956283/ DOI: 10.1182/blood-2005-03-1239

   tissue_or_cell_type

   Macrophage

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 398–409

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Measurement of Syk activation and reactive oxygen production in macrophage subpopulations · source_derived_draft · unverified_draft

   ### bg-syk-carries-the-oxidative-burst Dectin-1 activates Syk in macrophages and is important for Dectin-1-stimulated reactive oxygen production but not for phagocytosis, Syk activation is restricted to a subpopulation of macrophages that is in equilibrium with cells that cannot activate the pathway, and the proportion of macrophages using this signalling pathway can be modulated by cytokine treatment, so Dectin-1 signalling reveals dynamic macrophage heterogeneity in inflammatory activation potential. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: One kinase carries the oxidative burst but not the swallowing, and only some of the cells can run it at any moment. organism: Mouse tissue_or_cell_type: Macrophage experimental_model: Measurement of Syk activation and reactive oxygen production in macrophage subpopulations limitations: The heterogeneity finding is the important limit: the pathway operated in a subpopulation in equilibrium with cells that could not use it, and the proportion shifted with cytokine treatment. exposure: Dectin-1 stimulation with assessment of Syk activation, reactive oxygen production and phagocytosis evidence_span: {"source_cache": "artifacts/glucan-research/15956283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "05fbe0dae04d44d8af5946504f066c104e7a294b29d35d70463d50874ec7b41c", "start_char": 0, "end_char": 990, "text_sha256": "05fbe0dae04d44d8af5946504f066c104e7a294b29d35d70463d50874ec7b41c"} [bg-p15956283] Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. (2005). https://pubmed.ncbi.nlm.nih.gov/15956283/ DOI: 10.1182/blood-2005-03-1239

   Complete structured claim and evidence

5. Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera, treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection, in macrophages the GABAergic defense is mediated via macrophage type A GABA receptor, intracellular calcium release and the GABA type A receptor-associated protein-like 1, and GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo suggesting that the GABAergic defense plays an essential function in metazoan host defenses.

   Gamma-aminobutyric acid → Autophagy activation source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/gaba-research/30305619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d53b15743f61b910fb1db4781905673c81a070c12245068a369548544e3bc6e", "start_char": 0, "end_char": 1146, "text_sha256": "4d53b15743f61b910fb1db4781905673c81a070c12245068a369548544e3bc6e"}

   experimental_model

   Autophagy and phagosome assays in macrophages with receptor and protein dependency, and infection burden in two whole animals

   exposure

   GABA and GABAergic drugs during intracellular mycobacterial infection, with GABAergic inhibition in vivo

   limitations

   The dependency on the receptor and on a specific autophagy protein is tested, and the outcome is measured in two species. The direction is the opposite of the autoimmunity records.

   nutrient_topic

   GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

   organism

   Mouse and zebrafish

   plain_language

   Here the same molecule helps rather than suppresses: it drives the cell to digest the bacteria inside it, and blocking it lets the infection grow.

   primary_references

   [gb-p30305619] GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections. (2018). https://pubmed.ncbi.nlm.nih.gov/30305619/ DOI: 10.1038/s41467-018-06487-5

   tissue_or_cell_type

   Macrophage

   GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 586–597

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Autophagy and phagosome assays in macrophages with receptor and protein dependency, and infection burden in two whole animals · source_derived_draft · unverified_draft

   ### gb-gaba-helps-the-host-kill-bacteria Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera, treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection, in macrophages the GABAergic defense is mediated via macrophage type A GABA receptor, intracellular calcium release and the GABA type A receptor-associated protein-like 1, and GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo suggesting that the GABAergic defense plays an essential function in metazoan host defenses. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: Here the same molecule helps rather than suppresses: it drives the cell to digest the bacteria inside it, and blocking it lets the infection grow. organism: Mouse and zebrafish tissue_or_cell_type: Macrophage experimental_model: Autophagy and phagosome assays in macrophages with receptor and protein dependency, and infection burden in two whole animals limitations: The dependency on the receptor and on a specific autophagy protein is tested, and the outcome is measured in two species. The direction is the opposite of the autoimmunity records. exposure: GABA and GABAergic drugs during intracellular mycobacterial infection, with GABAergic inhibition in vivo evidence_span: {"source_cache": "artifacts/gaba-research/30305619.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4d53b15743f61b910fb1db4781905673c81a070c12245068a369548544e3bc6e", "start_char": 0, "end_char": 1146, "text_sha256": "4d53b15743f61b910fb1db4781905673c81a070c12245068a369548544e3bc6e"} [gb-p30305619] GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections. (2018). https://pubmed.ncbi.nlm.nih.gov/30305619/ DOI: 10.1038/s41467-018-06487-5

   Complete structured claim and evidence

6. GABA-A receptor subunits were expressed by primary lung macrophages of mice and the mouse macrophage cell line RAW264.7, the expression levels of these subunits decreased or increased concurrently with classical M1 or alternative M2 activation respectively, moreover activation or blockade of the receptors distinctively influenced the phenotypic characteristics of the macrophages, and these results suggested that microenvironments leading to macrophage phenotypic polarization concurrently modulate autocrine GABA signaling and its role in macrophage activation.

   Classical M1-like and alternative M2-like macrophage activation → GABA-A receptor anion channels source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/gaba-research/30017085.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c2d49008808726bf766218eb51ab5ec08e9790897619e750b8caacc1afad63b", "start_char": 0, "end_char": 1120, "text_sha256": "8c2d49008808726bf766218eb51ab5ec08e9790897619e750b8caacc1afad63b"}

   experimental_model

   Subunit expression and phenotype in primary lung macrophages and a macrophage cell line under polarising conditions

   exposure

   Classical and alternative activating conditions, with GABA-A receptor activation or blockade

   limitations

   Expression changes and phenotype rather than disease outcome. It shows the receptor tracks polarisation rather than that it drives it.

   nutrient_topic

   GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

   organism

   Mouse

   plain_language

   The receptor goes up as the cell takes the repair-type phenotype and down as it takes the inflammatory one.

   primary_references

   [gb-p30017085] Autocrine GABA signaling distinctively regulates phenotypic activation of mouse pulmonary macrophages. (2018). https://pubmed.ncbi.nlm.nih.gov/30017085/ DOI: 10.1016/j.cellimm.2018.07.001

   tissue_or_cell_type

   Lung macrophage

   GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 573–584

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Subunit expression and phenotype in primary lung macrophages and a macrophage cell line under polarising conditions · source_derived_draft · unverified_draft

   ### gb-the-receptor-tracks-polarisation GABA-A receptor subunits were expressed by primary lung macrophages of mice and the mouse macrophage cell line RAW264.7, the expression levels of these subunits decreased or increased concurrently with classical M1 or alternative M2 activation respectively, moreover activation or blockade of the receptors distinctively influenced the phenotypic characteristics of the macrophages, and these results suggested that microenvironments leading to macrophage phenotypic polarization concurrently modulate autocrine GABA signaling and its role in macrophage activation. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: The receptor goes up as the cell takes the repair-type phenotype and down as it takes the inflammatory one. organism: Mouse tissue_or_cell_type: Lung macrophage experimental_model: Subunit expression and phenotype in primary lung macrophages and a macrophage cell line under polarising conditions limitations: Expression changes and phenotype rather than disease outcome. It shows the receptor tracks polarisation rather than that it drives it. exposure: Classical and alternative activating conditions, with GABA-A receptor activation or blockade evidence_span: {"source_cache": "artifacts/gaba-research/30017085.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c2d49008808726bf766218eb51ab5ec08e9790897619e750b8caacc1afad63b", "start_char": 0, "end_char": 1120, "text_sha256": "8c2d49008808726bf766218eb51ab5ec08e9790897619e750b8caacc1afad63b"} [gb-p30017085] Autocrine GABA signaling distinctively regulates phenotypic activation of mouse pulmonary macrophages. (2018). https://pubmed.ncbi.nlm.nih.gov/30017085/ DOI: 10.1016/j.cellimm.2018.07.001

   Complete structured claim and evidence

7. GABA transporter GAT2 modulates macrophage function and GAT2 deficiency lowers the production of interleukin-1 beta in proinflammatory macrophages, mechanistically GAT2 deficiency boosts the betaine, S-adenosylmethionine and hypoxanthine metabolic pathway to inhibit transcription factor KID3 expression through increased DNA methylation in its promoter region, KID3 regulates oxidative phosphorylation via targeting the expression of related genes and is also critical for NLRP3-ASC-caspase-1 complex formation, and GAT2 deficiency attenuates macrophage-mediated inflammatory responses in vivo including lipopolysaccharide-induced sepsis, infection-induced pneumonia and high-fat diet-induced obesity.

   The GABA transporter GAT2 → Interleukin-1 beta / IL1B source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/gaba-research/33827820.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c654d761170222f117b179e232f555803d6a7cadcfb2eed7b95c45539787cff", "start_char": 0, "end_char": 1140, "text_sha256": "7c654d761170222f117b179e232f555803d6a7cadcfb2eed7b95c45539787cff"}

   experimental_model

   Transporter deficiency with metabolic pathway analysis, promoter methylation and three in vivo inflammatory models

   exposure

   GAT2 deficiency in macrophages, with lipopolysaccharide sepsis, infection-induced pneumonia and high-fat diet models

   limitations

   The mechanism assigned here is metabolic and transcriptional, running through methylation of a transcription factor promoter, rather than an electrophysiological one.

   nutrient_topic

   GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

   organism

   Mouse

   plain_language

   Taking away the carrier that moves GABA into the macrophage lowered its main inflammatory output, through a metabolic route and not an electrical one.

   primary_references

   [gb-p33827820] GABA transporter sustains IL-1β production in macrophages. (2021). https://pubmed.ncbi.nlm.nih.gov/33827820/ DOI: 10.1126/sciadv.abe9274

   tissue_or_cell_type

   Proinflammatory macrophage

   GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 560–571

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter deficiency with metabolic pathway analysis, promoter methylation and three in vivo inflammatory models · source_derived_draft · unverified_draft

   ### gb-the-transporter-sustains-il1b GABA transporter GAT2 modulates macrophage function and GAT2 deficiency lowers the production of interleukin-1 beta in proinflammatory macrophages, mechanistically GAT2 deficiency boosts the betaine, S-adenosylmethionine and hypoxanthine metabolic pathway to inhibit transcription factor KID3 expression through increased DNA methylation in its promoter region, KID3 regulates oxidative phosphorylation via targeting the expression of related genes and is also critical for NLRP3-ASC-caspase-1 complex formation, and GAT2 deficiency attenuates macrophage-mediated inflammatory responses in vivo including lipopolysaccharide-induced sepsis, infection-induced pneumonia and high-fat diet-induced obesity. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: Taking away the carrier that moves GABA into the macrophage lowered its main inflammatory output, through a metabolic route and not an electrical one. organism: Mouse tissue_or_cell_type: Proinflammatory macrophage experimental_model: Transporter deficiency with metabolic pathway analysis, promoter methylation and three in vivo inflammatory models limitations: The mechanism assigned here is metabolic and transcriptional, running through methylation of a transcription factor promoter, rather than an electrophysiological one. exposure: GAT2 deficiency in macrophages, with lipopolysaccharide sepsis, infection-induced pneumonia and high-fat diet models evidence_span: {"source_cache": "artifacts/gaba-research/33827820.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c654d761170222f117b179e232f555803d6a7cadcfb2eed7b95c45539787cff", "start_char": 0, "end_char": 1140, "text_sha256": "7c654d761170222f117b179e232f555803d6a7cadcfb2eed7b95c45539787cff"} [gb-p33827820] GABA transporter sustains IL-1β production in macrophages. (2021). https://pubmed.ncbi.nlm.nih.gov/33827820/ DOI: 10.1126/sciadv.abe9274

   Complete structured claim and evidence

8. Expression of endothelial nitric oxide synthase and nitrite concentrations were significantly increased in treated subjects, and treatment sensitised macrophages to release FGF-2 and EGF while increasing the neutrophil attractant CXCL-8 and thereby the release of CCL2.

   Hyperbaric oxygen therapy → Nitrite concentration in wound tissue source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"}

   experimental_model

   Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies

   exposure

   Hyperbaric oxygen with standard wound care for 20 days

   limitations

   A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue.

   nutrient_topic

   Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

   organism

   Human

   plain_language

   The same nitric oxide enzyme appears again, this time in the wound, with the immune cells joining in.

   primary_references

   [hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

   tissue_or_cell_type

   Diabetic foot ulcer tissue

   Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 842–853

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies · source_derived_draft · unverified_draft

   ### hbot-enos-nitrite-wound Expression of endothelial nitric oxide synthase and nitrite concentrations were significantly increased in treated subjects, and treatment sensitised macrophages to release FGF-2 and EGF while increasing the neutrophil attractant CXCL-8 and thereby the release of CCL2. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The same nitric oxide enzyme appears again, this time in the wound, with the immune cells joining in. organism: Human tissue_or_cell_type: Diabetic foot ulcer tissue experimental_model: Randomised comparison of 32 patients receiving standard wound care with or without hyperbaric oxygen, with ulcer tissue biopsies limitations: A small randomised human study with tissue-level molecular endpoints. Correlations between Nrf2 and growth factors are associations within treated tissue. exposure: Hyperbaric oxygen with standard wound care for 20 days evidence_span: {"source_cache": "artifacts/hbot-research/31035003.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc", "start_char": 0, "end_char": 1966, "text_sha256": "e0b19a857412f1a255ecc82052eb403389bcf5596a562828c04558e1d4354efc"} [hbot-p31035003] Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. (2019). https://pubmed.ncbi.nlm.nih.gov/31035003/ DOI: 10.1016/j.freeradbiomed.2019.04.031

   Complete structured claim and evidence