{"doi":"10.1172/jci138136","title":"Complement activation on endothelium initiates antibody-mediated acute lung injury","abstract":"Antibodies targeting human leukocyte antigen (HLA)/major histocompatibility complex (MHC) proteins limit successful transplantation and transfusion, and their presence in blood products can cause lethal transfusion-related acute lung injury (TRALI). It is unclear which cell types are bound by these anti-leukocyte antibodies to initiate an immunologic cascade resulting in lung injury. We therefore conditionally removed MHC class I (MHC I) from likely cellular targets in antibody-mediated lung injury. Only the removal of endothelial MHC I reduced lung injury and mortality, related mechanistically to absent endothelial complement fixation and lung platelet retention. Restoration of endothelial MHC I rendered MHC I-deficient mice susceptible to lung injury. Neutrophil responses, including neutrophil extracellular trap (NET) release, were intact in endothelial MHC I-deficient mice, whereas complement depletion reduced both lung injury and NETs. Human pulmonary endothelial cells showed high HLA class I expression, and posttransfusion complement activation was increased in clinical TRALI. These results indicate that the critical source of antigen for anti-leukocyte antibodies is in fact the endothelium, which reframes our understanding of TRALI as a rapid-onset vasculitis. Inhibition of complement activation may have multiple beneficial effects of reducing endothelial injury, platelet retention, and NET release in conditions where antibodies trigger these pathogenic responses.","journal":"Journal of Clinical Investigation","year":2020,"id":60989,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":322387,"name":"Nicholas Kwaan","orcid":"0000-0002-9763-9753","position":1,"is_corresponding":false},{"id":324443,"name":"Jennifer J. Tian","orcid":null,"position":2,"is_corresponding":false},{"id":311012,"name":"Daniel R. Calabrese","orcid":"0000-0002-0596-3434","position":3,"is_corresponding":false},{"id":312916,"name":"Beñat Mallavia","orcid":null,"position":4,"is_corresponding":false},{"id":322388,"name":"Mélia Magnen","orcid":"0000-0001-5189-0072","position":5,"is_corresponding":false},{"id":311020,"name":"John R. Greenland","orcid":"0000-0003-1422-8367","position":6,"is_corresponding":false},{"id":310704,"name":"Anatoly Urisman","orcid":"0000-0001-8364-5303","position":7,"is_corresponding":false},{"id":311016,"name":"Jonathan P. Singer","orcid":"0000-0003-0224-7472","position":8,"is_corresponding":false},{"id":311017,"name":"Steven R. Hays","orcid":"0000-0002-2887-8451","position":9,"is_corresponding":false},{"id":311018,"name":"Jasleen Kukreja","orcid":"0000-0003-2991-6680","position":10,"is_corresponding":false},{"id":297838,"name":"Ariel Hay","orcid":"0000-0002-9003-6415","position":11,"is_corresponding":false},{"id":324444,"name":"Heather L. Howie","orcid":null,"position":12,"is_corresponding":false},{"id":324445,"name":"Pearl Toy","orcid":null,"position":13,"is_corresponding":false},{"id":322389,"name":"Clifford A. Lowell","orcid":"0000-0002-0467-7073","position":14,"is_corresponding":false},{"id":251415,"name":"Craig N. Morrell","orcid":"0000-0001-9131-4862","position":15,"is_corresponding":false},{"id":110273,"name":"James C. Zimring","orcid":"0000-0002-1063-4010","position":16,"is_corresponding":false},{"id":251402,"name":"Mark R. Looney","orcid":"0000-0003-0241-9190","position":17,"is_corresponding":false},{"id":251403,"name":"Simon J. Cleary","orcid":"0000-0001-5573-6363","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T21:09:27.985420Z","pmid":"32730229","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}