Neutrophils and their Fc gamma receptors are essential in a mouse model of transfusion-related acute lung injury

J Clin Invest. 2006 Jun;116(6):1615-23. doi: 10.1172/JCI27238. Epub 2006 May 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / immunology
  • Blood Transfusion*
  • Cell Membrane Permeability
  • Disease Models, Animal
  • Genes, MHC Class I
  • Humans
  • Lung / cytology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Neutrophils / transplantation
  • Organ Size
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology*
  • Respiratory Distress Syndrome* / etiology
  • Respiratory Distress Syndrome* / immunology


  • Antibodies, Monoclonal
  • Receptors, IgG