leukotriene-b4 and Transfusion-Reaction

Transfusion-related acute lung injury (TRALI) is one of the most serious side-effects of transfusion. We report here the first two cases of TRALI caused by anti-Nak(a) (anti-CD36) antibody from a single blood donor. The aim of this study was to clarify the role of the anti-Nak(a) antibody in TRALI development.. Human lung microvascular endothelial cells were co-cultured with Nak(a)-positive monocytes and Nak(a)-positive platelets together with serum prepared from blood products of a TRALI-caused anti-Nak(a) antibody-carrying donor. Expressions of leukotriene B(4) (LTB(4)) and tumour necrosis factor alpha (TNF-alpha) in the co-culture supernatants were determined.. The expressions of LTB(4) and TNF-alpha were found to be markedly increased, particularly in the presence of both Nak(a)-positive monocytes and platelets. The expressions of these mediators were almost completed within 4 h after the initiation of co-culture. Monocyte contribution seemed to be stronger than that of platelets. In the absence of human lung microvascular endothelial, no significant LTB(4) or TNF-alpha release was observed.. Anti-Nak(a) antibody may be strongly implicated in lung microvascular endothelial dysfunctions that lead to TRALI in a monocyte- and platelet-dependent manner.

Topics: Acute Lung Injury; Antibodies; Antigens, Human Platelet; Blood Platelets; Coculture Techniques; Endothelium, Vascular; Humans; Leukotriene B4; Lung; Microcirculation; Monocytes; Transfusion Reaction; Tumor Necrosis Factor-alpha

Recently, evidence implicating the roles of the anti-human leucocyte antigen (HLA) class II antibody in the development of transfusion-related acute lung injury (TRALI), which is one of the most serious possible side effects of transfusion, has been accumulating. The aim of this study is to clarify the roles of the anti-HLA DR alloantibody in TRALI development. Cultured human lung microvascular endothelial (LME) cells were incubated with either HLA-DR15-positive or HLA-DR15-negative monocytes together with serum from a single multiparous donor previously implicated in a clinical case of TRALI and known to contain anti-HLA DR15 antibody. Production of soluble leukotriene B(4) (LTB(4)) was measured in the supernatant and found to be markedly increased in the presence of HLA-DR15-positive monocytes but not with the HLA-DR15-negative monocytes or in the absence of LME cells. The vascular cell adhesion molecule-1 expression in LME cells and leucocyte-function-associated molecule-1 (LFA-1) expression in HLA-DR15-positive monocytes were notably enhanced after combined culture of LME cells, HLA-DR15-positive monocytes and TRALI-inducing anti-HLA DR15 antibody-positive serum. In conclusion, anti-HLA DR alloantibodies may be implicated in LME dysfunction that leads to TRALI, in a monocyte-dependent manner.

Topics: Blood Grouping and Crossmatching; Cell Adhesion Molecules; Cells, Cultured; Coculture Techniques; Endothelial Cells; Female; Histocompatibility Antigens Class II; Histocompatibility Testing; HLA-DR Antigens; HLA-DR Serological Subtypes; Humans; Isoantibodies; Leukotriene B4; Lymphocyte Function-Associated Antigen-1; Monocytes; Respiratory Distress Syndrome; Transfusion Reaction; Vascular Cell Adhesion Molecule-1

Transfusion of PLT concentrates may cause TRALI, a life-threatening reaction that has been linked to the infusion of anti-WBC immunoglobulins or older, stored PLTs that contain bioactive lipids. We hypothesize that lipids generated during storage of PLTs cause TRALI in a two-event animal model.. Plasma from both whole-blood PLTs (WB-PLTs) and apheresis PLTs (A-PLTs) was isolated on Day 0 (D.0) and Day 5 (D.5) of storage and heat-treated before use. Rats were pretreated with saline or 2 mg per kg endotoxin (LPS), anesthetized, and the lungs were ventilated, isolated, and perfused with saline or 5-percent PLT plasma. Pulmonary artery pressure, pulmonary edema, and leukotriene B4 levels (perfusate) were measured.. Plasma from D.5, but not D.0, of the identical WB-PLT and A-PLT units caused injury in lungs from LPS-pretreated rats (LPS/D.5) evidenced by increases in pulmonary edema and leukotriene B4 (p < 0.05). Lipid extracts and purified lipids from D.5 PLT plasma also elicited injury in lungs from LPS-pretreated rats (p < 0.05). Saline/D.5 plasma or lipids or LPS/D.0 did not cause pulmonary edema. Prestorage WBC reduction was ineffective in inhibiting TRALI.. PLT-induced TRALI may be the result of two events: 1) the clinical condition of the patient and 2) the infusion of lipids in stored PLTs.

Topics: Acute Disease; Adult; Animals; Blood Physiological Phenomena; Blood Platelets; Blood Preservation; Blood Pressure; Humans; In Vitro Techniques; Leukapheresis; Leukotriene B4; Lipids; Lung; Lung Diseases; Male; Perfusion; Pulmonary Artery; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Transfusion Reaction