{"id":"17da1574-dde5-5dd2-8ee9-fddca0021626","stable_key":"10629adf-a816-5b7b-82db-a76bfbb946f2:bg-macrophages-carry-and-cut-it","predicate":"produces","statement":"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.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"c9b9a84c-e317-5220-8ce0-6d01095e9b34","mechanism_event_label":"Swallowed glucan is carried to the marrow inside macrophages, cut up there, and handed to granulocytes on the way out.","subject":{"id":"e41135e7-f6e8-5b9d-b46e-9a05a3be19e0","slug":"macrophage-trafficking","display_name":"Transport of ingested glucan by macrophages to spleen, lymph node and marrow","entity_type_key":"cellular_process"},"object":{"id":"c78de9b6-93fd-5ae1-8894-78b1c410c160","slug":"beta-glucan-oligosaccharide","display_name":"Beta-(1->3)-linked gluco-oligosaccharides","entity_type_key":"chemical_species"},"evidence_count":1,"mechanism_event":{"id":"c9b9a84c-e317-5220-8ce0-6d01095e9b34","stable_key":"10629adf-a816-5b7b-82db-a76bfbb946f2:bg-macrophages-carry-and-cut-it-event","event_type":"biochemical_relationship","label":"Swallowed glucan is carried to the marrow inside macrophages, cut up there, and handed to granulocytes on the way out.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a15f1036-2f04-5ebc-a9a3-0e8fed521f99","slug":"macrophage","display_name":"Macrophage","entity_type_key":"cell_type"},"role":"transporting_cell","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a1abb369-49cb-512c-9807-1591b9307567","slug":"granulocyte","display_name":"Granulocyte","entity_type_key":"cell_type"},"role":"receiving_cell","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"309b5460-2ec8-5c78-ada2-8637d6991433","slug":"cr3-complex","display_name":"Complement receptor 3 / CD11b-CD18","entity_type_key":"protein_complex"},"role":"receiving_receptor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"fca72f53-5c06-5fcb-8a0b-f48514e63762","slug":"glucan-depolymerisation","display_name":"Depolymerisation of a glucan polymer","entity_type_key":"cellular_process"},"role":"required_step","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"7e39f8b2-8b39-5f3b-bb37-ca39a7f72221","slug":"tumour-cell-killing","display_name":"Killing of antibody-opsonised tumour cells by leukocytes","entity_type_key":"cellular_process"},"role":"downstream_process","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"e41135e7-f6e8-5b9d-b46e-9a05a3be19e0","slug":"macrophage-trafficking","display_name":"Transport of ingested glucan by macrophages to spleen, lymph node and marrow","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"c78de9b6-93fd-5ae1-8894-78b1c410c160","slug":"beta-glucan-oligosaccharide","display_name":"Beta-(1->3)-linked gluco-oligosaccharides","entity_type_key":"chemical_species"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"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\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Fluorescein-labelled oral glucans tracked through macrophages to marrow, with therapy in C3-deficient and CR3-deficient mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Orally administered barley beta-1,3;1,4-glucan and orally administered yeast beta-1,3;1,6-glucan, each with antitumour monoclonal antibody","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":{"slug":"beta-glucan","display_name":"Beta-glucan","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Swallowed glucan is carried to the marrow inside macrophages, cut up there, and handed to granulocytes on the way out.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Gut, spleen, lymph node, bone marrow and tumour","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"a9169d0f-0303-5bf4-a476-838a9e3fef16","evidence_kind":"source_excerpt","locator":"Lines 255-266","start_line":255,"end_line":266,"excerpt":"### bg-macrophages-carry-and-cut-it\nBarley 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.\nCondition category: normal\nnutrient_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.\nplain_language: Swallowed glucan is carried to the marrow inside macrophages, cut up there, and handed to granulocytes on the way out.\norganism: Mouse\ntissue_or_cell_type: Gut, spleen, lymph node, bone marrow and tumour\nexperimental_model: Fluorescein-labelled oral glucans tracked through macrophages to marrow, with therapy in C3-deficient and CR3-deficient mice\nlimitations: 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.\nexposure: Orally administered barley beta-1,3;1,4-glucan and orally administered yeast beta-1,3;1,6-glucan, each with antitumour monoclonal antibody\nevidence_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\"}\n[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","model_system":"Fluorescein-labelled oral glucans tracked through macrophages to marrow, with therapy in C3-deficient and CR3-deficient mice","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study 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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"74dc223d-8289-57bf-a731-d220fa017c1e","stable_key":"import-10629adf-a816-5b7b-82db-a76bfbb946f2","title":"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)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"7c62f2d2f8d99b650e6dc26a505b0f053ae1c8bdb38099d4dfc0771f65287461","revision_id":"a53bb794-0a4b-525d-9cf7-22b46a5403b0","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"e601d23c-8004-599e-a54b-d0540ce1fd7d","title":"Does an oral beta-glucan produce a systemic effect?","kind":"contradiction","status":"open","why":"In rodents it plainly does. Three water-soluble glucans given by mouth appeared in plasma with measurable peaks, were internalised by intestinal epithelium and gut-associated lymphoid tissue, raised gut-associated Dectin-1 and TLR2 expression, raised systemic interleukin-12 by 151% and improved survival against two organisms. A separate mouse study tracked labelled oral glucan through macrophages to the marrow and showed granulocytes acquiring the processed fragments. In the one human oral dosing study recorded here, a gram a day for seven days left beta-glucan barely detectable in serum and changed neither ex vivo cytokine production nor microbicidal activity. The human study is a fifteen-person open-label pilot of one product at one dose with ex vivo readouts, so it is not a refutation of every oral preparation; equally, the rodent work cannot be read across to people, and the two oncology trials here that used oral glucan measured clinical and antibody endpoints rather than systemic exposure. What the records jointly establish is that oral bioavailability and systemic effect are preparation-specific and species-specific questions that have to be measured rather than assumed.","resolution":"Unresolved. The rodent and human records differ in species, preparation, dose and endpoint simultaneously, and no study here bridges them.","created_at":"2026-09-22 23:28:00","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/e601d23c-8004-599e-a54b-d0540ce1fd7d","sides":[{"conflict_id":"e601d23c-8004-599e-a54b-d0540ce1fd7d","ordinal":0,"label":"In rodents the swallowed sugar does cross into the circulation, is taken up by the gut immune tissue, and leaves the animals better able to survive an infection.","revision_id":"a53bb794-0a4b-525d-9cf7-22b46a5403b0","start_line":372,"end_line":383,"quote":"### bg-oral-glucan-does-reach-the-blood\nMaximum plasma concentrations for glucan phosphate occurred at 4 hours while laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 hours, at 24 hours 27 plus or minus 3% of the glucan phosphate and 20 plus or minus 7% of the laminarin remained in the serum, following oral administration glucans were bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue cells with internalization by intestinal epithelial cells not being Dectin-dependent, gut-associated lymphoid tissue expression of Dectin-1 and Toll-like receptor 2 but not Toll-like receptor 4 increased, oral glucan increased systemic levels of interleukin-12 by 151%, and oral glucan administration also increased survival in mice challenged with Staphylococcus aureus or Candida albicans.\nCondition category: normal\nnutrient_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.\nplain_language: In rodents the swallowed sugar does cross into the circulation, is taken up by the gut immune tissue, and leaves the animals better able to survive an infection.\norganism: Rat and mouse\ntissue_or_cell_type: Plasma, intestinal epithelium and gut-associated lymphoid tissue\nexperimental_model: Oral pharmacokinetics of three water-soluble glucans in rats, with uptake, receptor expression and infectious challenge in mice\nlimitations: Rodent pharmacokinetics and rodent challenge models. The reported figure for glucan phosphate at 24 hours is a percentage remaining in serum whose denominator the abstract does not state, so it is not read here as a fraction of the swallowed dose.\nexposure: Glucan phosphate, laminarin and scleroglucan at 1 milligram per kilogram orally in rats, and 1 milligram orally in mice\nevidence_span: {\"source_cache\": \"artifacts/glucan-research/15976018.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"19df013d426cc48180a1bc6bb1e1e359c1d8b1f923cc97be369f5ad9116c3b18\", \"start_char\": 0, \"end_char\": 1617, \"text_sha256\": \"19df013d426cc48180a1bc6bb1e1e359c1d8b1f923cc97be369f5ad9116c3b18\"}\n[bg-p15976018] Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. (2005). https://pubmed.ncbi.nlm.nih.gov/15976018/ DOI: 10.1124/jpet.105.085415","source_key":"import-10629adf-a816-5b7b-82db-a76bfbb946f2","source_title":"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)","claim_ids":["70d1c8b7-86c0-5b47-84a9-6d673f177719"]},{"conflict_id":"e601d23c-8004-599e-a54b-d0540ce1fd7d","ordinal":1,"label":"Ten healthy men took a gram a day for a week; almost none of it showed up in the blood and nothing measurable changed.","revision_id":"a53bb794-0a4b-525d-9cf7-22b46a5403b0","start_line":385,"end_line":396,"quote":"### bg-in-people-nothing-was-detectable\nIn a randomised open-label intervention pilot study in 15 healthy male volunteers, subjects in the beta-glucan group ingested beta-glucan 1000 milligrams once daily for 7 days, beta-glucan was barely detectable in serum of volunteers at all time-points, and neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered beta-glucan, so the present study does not support the use of oral beta-glucan to enhance innate immune responses in humans.\nCondition category: normal\nnutrient_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.\nplain_language: Ten healthy men took a gram a day for a week; almost none of it showed up in the blood and nothing measurable changed.\norganism: Human\ntissue_or_cell_type: Serum and peripheral leukocytes\nexperimental_model: Randomised open-label intervention pilot study in 15 healthy male volunteers\nlimitations: Ten treated and five control subjects, one product, one dose, seven days, and ex vivo readouts. A negative pilot of this size does not establish that all oral preparations are inactive.\nexposure: Oral beta-glucan 1000 milligrams once daily for 7 days against no treatment, with serial sampling\nevidence_span: {\"source_cache\": \"artifacts/glucan-research/25268806.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b5a583c465284aae8e7d3e6dd9996fafe3b6ef389c61ee2a54f066fb4701e51b\", \"start_char\": 0, \"end_char\": 1307, \"text_sha256\": \"b5a583c465284aae8e7d3e6dd9996fafe3b6ef389c61ee2a54f066fb4701e51b\"}\n[bg-p25268806] The effects of orally administered Beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study. (2014). https://pubmed.ncbi.nlm.nih.gov/25268806/ DOI: 10.1371/journal.pone.0108794","source_key":"import-10629adf-a816-5b7b-82db-a76bfbb946f2","source_title":"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)","claim_ids":["9abf73e9-9b19-5876-9a86-89cb23d2ae4b"]},{"conflict_id":"e601d23c-8004-599e-a54b-d0540ce1fd7d","ordinal":2,"label":"Swallowed glucan is carried to the marrow inside macrophages, cut up there, and handed to granulocytes on the way out.","revision_id":"a53bb794-0a4b-525d-9cf7-22b46a5403b0","start_line":255,"end_line":266,"quote":"### bg-macrophages-carry-and-cut-it\nBarley 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.\nCondition category: normal\nnutrient_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.\nplain_language: Swallowed glucan is carried to the marrow inside macrophages, cut up there, and handed to granulocytes on the way out.\norganism: Mouse\ntissue_or_cell_type: Gut, spleen, lymph node, bone marrow and tumour\nexperimental_model: Fluorescein-labelled oral glucans tracked through macrophages to marrow, with therapy in C3-deficient and CR3-deficient mice\nlimitations: 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.\nexposure: Orally administered barley beta-1,3;1,4-glucan and orally administered yeast beta-1,3;1,6-glucan, each with antitumour monoclonal antibody\nevidence_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\"}\n[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","source_key":"import-10629adf-a816-5b7b-82db-a76bfbb946f2","source_title":"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)","claim_ids":["17da1574-dde5-5dd2-8ee9-fddca0021626"]}]}],"corrections":[],"research":null}