title: Lung microvascular endothelial cell injury caused by treatment with polymorphonuclear neutrophils and low-IgM serum: a model of transfusion-related acute lung injury.
abstract: Transfusion-related acute lung injury (TRALI) is one of the serious side effects that occur immediately after blood transfusion. The etiology of TRALI may be attributed to the presence of anti-human leukocyte antigen (HLA) and/or anti-polymorphonuclear neutrophil (PMN) antibodies in the plasma of donor blood products. However, the precise mechanisms underlying the development of TRALI are unclear to date. To further evaluate mechanisms we investigated the relationship between human lung microvascular endothelial cell (LME cell) lysis and normal human serum. We found the LME cell lysis occurred within 4 h of combining LME cells with PMNs and low-IgM serum, but not with high-IgM serum, without serum, or with PMNs alone. By flow cytometry and modified ELISA, the specific binding of not only PMN surface proteins but also intact PMNs to LME cells was observed in the presence of low-IgM serum but not in the presence of high-IgM serum or in the absence of serum. The blocking of CD7 expressed on LME cells or the blocking of CD16 or CD32 on PMNs by pretreatment with monoclonal antibodies (mAbs) inhibited LME cell lysis. Moreover, two serum samples with low lgM obtained from blood donors whose sera contained anti-PMN antibodies caused LME cell lysis in the presence of PMNs. Furthermore, the addition of an elastase inhibitor inhibited the lysis of LME cells caused by the treatment with PMNs and low-IgM serum. Our present results suggest that PMNs and low-IgM serum are the likely components in the development of TRALI.
authors.affiliation: Research Section, Tokyo Metropolitan Red Cross Blood Center, 4-1-31 Hiro-o, Tokyo, 150-0012. mo-nishimura@tokyo.bc.jrc.or.jp
authors.forename: Motoko
authors.initials: M
authors.lastname: Nishimura
authors.forename: Minoko
authors.initials: M
authors.lastname: Takanashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Satake
mesh_terms: D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D008168:Lung / Q000166:cytology / Q000473:pathology*; D009504:Neutrophils / Q000378:metabolism*; D065227:Transfusion Reaction
chemical_list: D007075:Immunoglobulin M