title: Possible mechanisms underlying development of transfusion-related acute lung injury: roles of anti-major histocompatibility complex class II DR antibody.
abstract: Anti-major histocompatibility complex (anti-MHC) antibodies (Abs) and antipolymorphonuclear neutrophil (anti-PMN) Abs are generally considered as the main causes of the development of transfusion-related acute lung injury (TRALI), which is one of the most severe and sometimes lethal side effects of transfusion. These Abs are postulated to activate recipient's leucocytes, resulting in the release of soluble factors such as reactive oxygen species and detrimental cytokines and chemokines. The harmful effects on the lung tissues and resident leucocytes of these malignant factors are suspected to be profoundly involved in TRALI reactions. Several reports have indicated the principle effect of biologically active lipids on the pathogenesis of TRALI. However, the precise mechanisms of TRALI development remain unclear. To resolve this issue, we have been investigating cytokines that induce continuous inflammation of the lungs, specifically focusing on the cytokines derived from activated PMNs. We observed that the granulocyte-macrophage colony-stimulating factor (GM-CSF) markedly enhances the expression of MHC class II DR in PMNs. Moreover, MHC class II DR-expressing PMNs were also proved to express a high-affinity receptor for immunoglobulin E (IgE) (FcepsilonRI) and to produce tumour necrosis factor-alpha, interferon-gamma and interleukin-18 following a challenge with an anti-MHC class II DR monoclonal Ab (MoAb) or anti-DR antiserum. It is strongly suggested that amongst various inflammatory mediators, at least these three cytokines may contribute to the duration of inflammatory reactions in the lungs. Furthermore, FcepsilonRI expression, in GM-CSF-treated PMNs, suggests the involvement of PMNs in IgE-mediated immune reactions.
authors.affiliation: Department of Research, Tokyo Metropolitan Red Cross Blood Center, Tokyo, Japan. mo-nishimura@tokyo.bc.jrc.or.jp
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: S
authors.initials: S
authors.lastname: Mitsunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: M
authors.initials: M
authors.lastname: Satake
mesh_terms: D016207:Cytokines / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D007518:Isoantibodies / Q000276:immunology* / Q000494:pharmacology; D018375:Neutrophil Activation / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology*; D065227:Transfusion Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D007518:Isoantibodies; D017455:Receptors, IgE; D016178:Granulocyte-Macrophage Colony-Stimulating Factor