PMID- 21030555 OWN - NLM STAT- MEDLINE DCOM- 20110223 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 117 IP - 2 DP - 2011 Jan 13 TI - Mechanism of transfusion-related acute lung injury induced by HLA class II antibodies. PG - 669-77 LID - 10.1182/blood-2010-05-286146 [doi] AB - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the United States and other countries. In most TRALI cases, human leukocyte antigen (HLA) class II antibodies are detected in implicated donors. However, the corresponding antigens are not present on the cellular key players in TRALI: neutrophils and endothelium. In this study, we identify monocytes as a primary target in HLA class II-induced TRALI. Monocytes become activated when incubated with matched HLA class II antibodies and are capable of activating neutrophils, which, in turn, can induce disturbance of an endothelial barrier. In an ex vivo rodent model, HLA class II antibody-dependent monocyte activation leads to severe pulmonary edema in a relevant period of time, whenever neutrophils are present and the endothelium is preactivated. Our data suggest that in most TRALI cases, monocytes are cellular key players, because HLA class II antibodies induce TRALI by a reaction cascade initiated by monocyte activation. Furthermore, our data support the previous assumption that TRALI pathogenesis follows a threshold model. Having identified the biologic mechanism of HLA class II antibody-induced TRALI, strategies to avoid plasma from immunized donors, such as women with a history of pregnancy, appear to be justified preventive measures. FAU - Sachs, Ulrich J H AU - Sachs UJ AD - Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany. ulrich.sachs@med.uni-giessen.de FAU - Wasel, Wiebke AU - Wasel W FAU - Bayat, Behnaz AU - Bayat B FAU - Bohle, Rainer M AU - Bohle RM FAU - Hattar, Katja AU - Hattar K FAU - Berghofer, Heike AU - Berghofer H FAU - Reil, Angelika AU - Reil A FAU - Bux, Jurgen AU - Bux J FAU - Bein, Gregor AU - Bein G FAU - Santoso, Sentot AU - Santoso S FAU - Weissmann, Norbert AU - Weissmann N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101028 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Isoantibodies) RN - 0 (Isoantigens) SB - IM CIN - Blood. 2011 Jan 13;117(2):378-9. PMID: 21233322 MH - Acute Lung Injury/blood/*immunology MH - Animals MH - Capillary Permeability/immunology MH - Cell Separation MH - Female MH - Flow Cytometry MH - Histocompatibility Antigens Class II/*immunology MH - Humans MH - Isoantibodies/blood/immunology MH - Isoantigens/immunology MH - Male MH - Monocytes/*immunology MH - Neutrophil Activation/immunology MH - Neutrophils/immunology MH - Rats MH - *Transfusion Reaction EDAT- 2010/10/30 06:00 MHDA- 2011/02/24 06:00 CRDT- 2010/10/30 06:00 PHST- 2010/10/30 06:00 [entrez] PHST- 2010/10/30 06:00 [pubmed] PHST- 2011/02/24 06:00 [medline] AID - S0006-4971(20)59216-1 [pii] AID - 10.1182/blood-2010-05-286146 [doi] PST - ppublish SO - Blood. 2011 Jan 13;117(2):669-77. doi: 10.1182/blood-2010-05-286146. Epub 2010 Oct 28.