Neutrophils and their Fc gamma receptors are essential in a mouse model of transfusion-related acute lung injury.
Transfusion-related acute lung injury (TRALI) is the most common cause of transfusion-related mortality. To explore the pathogenesis of TRALI, we developed an in vivo mouse model based on the passive transfusion of an MHC class I (MHC I) mAb (H2Kd) to mice with the cognate antigen. Transfusion of the MHC I mAb to BALB/c mice produced acute lung injury with increased excess lung water, increased lung vascular and lung epithelial permeability to protein, and decreased alveolar fluid clearance. There was 50% mortality at a 2-hour time point after Ab administration. Pulmonary histology and immunohistochemistry revealed prominent neutrophil sequestration in the lung microvasculature that occurred concomitantly with acute peripheral blood neutropenia, all within 2 hours of administration of the mAb. Depletion of neutrophils by injection of anti-granulocyte mAb Gr-1 protected mice from lung injury following MHC I mAb challenge. FcRgamma-/- mice were resistant to MHC I mAb-induced lung injury, while adoptive transfer of wild-type neutrophils into the FcRgamma-/- animals restored lung injury following MHC I mAb challenge. In conclusion, in a clinically relevant in vivo mouse model of TRALI using an MHC I mAb, the mechanism of lung injury was dependent on neutrophils and their Fc gamma receptors.
Looney
Mark R
MR
Cardiovascular Research Institute, Department of Medicine, UCSF, San Francisco, California, USA. mark.looney@ucsf.edu
Su
Xiao
X
Van Ziffle
Jessica A
JA
Lowell
Clifford A
CA
Matthay
Michael A
MA
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001803:Blood Transfusion; D002463:Cell Membrane Permeability; D004195:Disease Models, Animal; D005805:Genes, MHC Class I; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D009929:Organ Size; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology
D000911:Antibodies, Monoclonal; D017452:Receptors, IgG