Acute passive anti-glomerular basement membrane nephritis in P-selectin-deficient mice

Kidney Int. 1996 May;49(5):1342-9. doi: 10.1038/ki.1996.190.


P-selectin present on surfaces of activated endothelium and platelets mediates neutrophil-endothelial and neutrophilplatelet interactions. The role of P-selectin in vivo was examined in a model of acute passive anti-GBM nephritis in P-selectin-deficient and wild-type mice which was induced by intravenous injection of anti-GBM serum. There were two major differences between P-selectin-deficient and wild-type mice. Firstly, mutant mice had approximately two fold more glomerular PMNs and albuminuria than wild-type animals at the peak of neutrophil influx and proteinuria. Secondly, Lipoxin A4 (LXA4), an eicosanoid which inhibits leukocyte-endothelial adhesion in vitro, and is generated primarily by transcellular biosynthetic routes during P-selectin-mediated platelet-PMN interaction [1], was approximately 60% of wild type levels in nephritic kidneys of P-selectin-deficient mice. Injection of wild-type platelets into P-selectin-null mice restored LXA4 to wild-type levels. The corresponding PMN influx approximated PMN levels in wild-type mice receiving platelets but urine albuminuria remained higher. Although these two P-selectin-dependent events cannot be directly linked, our results point to the importance of considering both platelet and endothelial P-selectin in determining the cellular events in inflammation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Basement Membrane / immunology
  • Blood Platelets / metabolism
  • Disease Models, Animal
  • Eicosanoids / metabolism
  • Female
  • Glomerulonephritis / etiology*
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology
  • Hydroxyeicosatetraenoic Acids / biosynthesis
  • Immunization, Passive
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Lipoxins*
  • Lipoxygenase / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Neutrophils / pathology
  • P-Selectin / metabolism*
  • Proteinuria / etiology


  • Eicosanoids
  • Hydroxyeicosatetraenoic Acids
  • Lipoxins
  • P-Selectin
  • lipoxin A4
  • Lipoxygenase