{"id":"9fcc3e2f-1151-58e5-badf-9c1d9d6b5f17","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-neutrophil-density","predicate":"increases","statement":"Repeated caffeine exposure increased neutrophil A2A receptor binding density.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"2dde36a7-b961-5647-98f0-6739db2d4be7","mechanism_event_label":"Repeated exposure changed receptor abundance in immune cells.","subject":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"object":{"id":"960bea79-fe75-5227-a556-c0947d94aef6","slug":"neutrophil-a2a-receptor-density","display_name":"Human neutrophil A2A receptor density","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2dde36a7-b961-5647-98f0-6739db2d4be7","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-neutrophil-density-event","event_type":"observed_relationship","label":"Repeated exposure changed receptor abundance in immune cells.","description":"Repeated caffeine exposure increased neutrophil A2A receptor binding density.","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":"960bea79-fe75-5227-a556-c0947d94aef6","slug":"neutrophil-a2a-receptor-density","display_name":"Human neutrophil A2A receptor density","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":""}]},"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":"Repeated exposure changed receptor abundance in immune cells.","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":"54108cb8-07a4-5ae3-83f1-df34e5ceb980","evidence_kind":"source_excerpt","locator":"Lines 148-154","start_line":148,"end_line":154,"excerpt":"## caf-neutrophil-density\nRepeated exposure changed receptor abundance in immune cells.\nRepeated caffeine exposure increased neutrophil A2A receptor binding density.\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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