title: Mac1+/Gr1+ cells contribute to transfusion-related acute lung injury.
abstract: Transfusion-related acute lung injury (TRALI) is a serious complication associated with blood transfusion and can cause transfusion associated fatalities. Both antibody dependent and non-dependent mechanisms are involved in TRALI, as proposed over the past years. Nonetheless, many details of the immune cells involved in TRALI, particularly the Mac1(+)/Gr1(+) cells from donors, are not fully understood yet. Here we used an in vitro transwell system and a mouse model to study the role of donor leukocytes, present in the donor material, in the occurrence of TRALI reactions. We found that there is a number of immature myeloid cells with Mac1(+)/Gr1(+) phenotype present in the red blood cell (RBC) products, when prepared by regular methods. We found that murine Mac1(+)/Gr1(+) cells from stored RBC products display an elevated MHC I and CD40 expression, as well as an enhanced tumor necrosis factor alpha(TNF-α), interlukin-6(IL-6) and macrophage inflammatory protein 2 (MIP-2) secretion. When tested in a transwell endothelial migration assay, Mac1(+)/Gr1(+) cells showed a significant capability to cross the endothelial barrier. In vivo investigation demonstrated that compared to the purified RBC transfusion, more murine Mac1(+)/Gr1(+) cells from the regular method produced RBC sequestered in the lung, which associated to shorter survival. Taken together, these data suggest that donor derived Mac1(+)/Gr1(+) cells can play a significant role in TRALI reactions, and that reduction of Mac1(+)/Gr1(+) cell number from RBC products is necessary to control the severity of TRALI reactions in clinic.
authors.affiliation: Department of Blood Transfusion, Xijing Hospital, The Fourth Military Medical University, 17th Changlexi Road, Xi'an 710032, China. Electronic address: hxbyqh@fmmu.edu.cn.
authors.forename: Xing-bin
authors.initials: XB
authors.lastname: Hu
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Yin
authors.forename: Yao-zhen
authors.initials: YZ
authors.lastname: Chen
authors.forename: Hai-feng Ou
authors.initials: HF
authors.lastname: Yang
authors.forename: Xian-qing
authors.initials: XQ
authors.lastname: Zhang
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001782:Blood Donors; D039481:CD11b Antigen / Q000096:biosynthesis / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D023421:Models, Animal; D022423:Myeloid Cells / Q000276:immunology*; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D065227:Transfusion Reaction; D055815:Young Adult
chemical_list: D000906:Antibodies; D039481:CD11b Antigen; D016207:Cytokines; D019707:Receptors, Chemokine
keywords: Cytokine; Mac1(+)/Gr1(+) cell; Red blood cell transfusion; TRALI