{"id":"da949576-575a-5405-955e-3172b6a89acb","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-neutrophil-superoxide","predicate":"alters_subsequent_agonist_response","statement":"NECA-stimulated adapted neutrophils showed lower superoxide production; binding and functional changes returned to baseline after 48 hours withdrawal.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"cc6cb5fe-a672-5702-bba6-dcfdc3fd315b","mechanism_event_label":"The immune-cell response was reversible and depended on the agonist challenge.","subject":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"object":{"id":"0b7e39ee-7dea-53c9-b9c6-f2ef13dd9643","slug":"neutrophil-neca-superoxide-response","display_name":"Human neutrophil superoxide response after NECA stimulation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cc6cb5fe-a672-5702-bba6-dcfdc3fd315b","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-neutrophil-superoxide-event","event_type":"observed_relationship","label":"The immune-cell response was reversible and depended on the agonist challenge.","description":"NECA-stimulated adapted neutrophils showed lower superoxide production; binding and functional changes returned to baseline after 48 hours withdrawal.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0b7e39ee-7dea-53c9-b9c6-f2ef13dd9643","slug":"neutrophil-neca-superoxide-response","display_name":"Human neutrophil superoxide response after NECA stimulation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6bebe966-e8de-5a69-aa15-8e651fc58e10","slug":"adora2a","display_name":"Human adenosine A2A receptor / ADORA2A","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"459bd59a-6653-5920-880f-bd1b259349c0","slug":"neca","display_name":"5′-N-Ethylcarboxamidoadenosine / NECA","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"011511ed-2be5-566d-bd1b-9d580dab1e9c","slug":"superoxide-anion","display_name":"Superoxide radical anion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human neutrophils after 400 or 600 mg/day for one week, or 400 mg/day for two weeks; ex-vivo binding and NECA challenges.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Adapted cells were challenged with an agonist; this is not the same as an immediate effect of caffeine, nor a clinical anti-inflammatory trial.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Caffeine collection; salts, coffee, species and coexposure contexts retain their identities.","comparator":null,"unit":null,"notes":"","entity":{"slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The immune-cell response was reversible and depended on the agonist challenge.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Caffeine intake induces an alteration in human neutrophil A2A adenosine receptors. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16143823/ · DOI 10.1007/s00018-005-5312-z","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ce42fda0-8eea-5605-9ff0-61199e9660de","evidence_kind":"source_excerpt","locator":"Lines 164-170","start_line":164,"end_line":170,"excerpt":"## caf-neutrophil-superoxide\nThe immune-cell response was reversible and depended on the agonist challenge.\nNECA-stimulated adapted neutrophils showed lower superoxide production; binding and functional changes returned to baseline after 48 hours withdrawal.\nModel: Human neutrophils after 400 or 600 mg/day for one week, or 400 mg/day for two weeks; ex-vivo binding and NECA challenges.\nLimitations: Adapted cells were challenged with an agonist; this is not the same as an immediate effect of caffeine, nor a clinical anti-inflammatory trial.\nEvidence access: Primary abstract\nCaffeine intake induces an alteration in human neutrophil A2A adenosine receptors. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16143823/ · DOI 10.1007/s00018-005-5312-z","model_system":"Human neutrophils after 400 or 600 mg/day for one week, or 400 mg/day for two weeks; ex-vivo binding and NECA challenges.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access stated with the claim.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"40a654db-878c-5471-bc6c-88f4f52599c0","stable_key":"import-ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6","title":"Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. 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