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Blood. 2014 May 29;123(22):3496-503. doi: 10.1182/blood-2013-11-536755. Epub 2014 Mar 17.

Peripheral blood monocyte-derived chemokine blockade prevents murine transfusion-related acute lung injury (TRALI).

Author information

  • 1Toronto Platelet Immunobiology Group, Toronto, ON, Canada; Keenan Center for Biomedical Research, St. Michael's Hospital, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and.
  • 2Toronto Platelet Immunobiology Group, Toronto, ON, Canada; Keenan Center for Biomedical Research, St. Michael's Hospital, Toronto, ON, Canada;
  • 3Toronto Platelet Immunobiology Group, Toronto, ON, Canada;
  • 4Toronto Platelet Immunobiology Group, Toronto, ON, Canada; Departments of Medicine.
  • 5Toronto Platelet Immunobiology Group, Toronto, ON, Canada; Keenan Center for Biomedical Research, St. Michael's Hospital, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada; and Departments of Medicine, Pharmacology, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Abstract

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and can occur with any type of transfusion. TRALI is thought to be primarily mediated by donor antibodies activating recipient neutrophils resulting in pulmonary endothelial damage. Nonetheless, details regarding the interactions between donor antibodies and recipient factors are unknown. A murine antibody-mediated TRALI model was used to elucidate the roles of the F(ab')2 and Fc regions of a TRALI-inducing immunoglobulin G anti-major histocompatibility complex (MHC) class I antibody (34.1.2s). Compared with intact antibody, F(ab')2 fragments significantly increased serum levels of the neutrophil chemoattractant macrophage inflammatory protein 2 (MIP-2); however, pulmonary neutrophil levels were only moderately increased, and no pulmonary edema or mortality occurred. Fc fragments did not modulate any of these parameters. TRALI induction by intact antibody was completely abrogated by in vivo peripheral blood monocyte depletion by gadolinium chloride (GdCl3) or chemokine blockade with a MIP-2 receptor antagonist but was restored upon repletion with purified monocytes. The results suggest a two-step process for antibody-mediated TRALI induction: the first step involves antibody binding its cognate antigen on blood monocytes, which generates MIP-2 chemokine production that is correlated with pulmonary neutrophil recruitment; the second step occurs when antibody-coated monocytes increase Fc-dependent lung damage.

© 2014 by The American Society of Hematology.

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PMID:
24637362
[PubMed - indexed for MEDLINE]
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