title: Acute passive anti-glomerular basement membrane nephritis in P-selectin-deficient mice.
abstract: 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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: T N
authors.initials: TN
authors.lastname: Mayadas
authors.forename: D L
authors.initials: DL
authors.lastname: Mendrick
authors.forename: H R
authors.initials: HR
authors.lastname: Brady
authors.forename: T
authors.initials: T
authors.lastname: Tang
authors.forename: A
authors.initials: A
authors.lastname: Papayianni
authors.forename: K J
authors.initials: KJ
authors.lastname: Assmann
authors.forename: D D
authors.initials: DD
authors.lastname: Wagner
authors.forename: R O
authors.initials: RO
authors.lastname: Hynes
authors.forename: R S
authors.initials: RS
authors.lastname: Cotran
mesh_terms: D000208:Acute Disease; D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D001792:Blood Platelets / Q000378:metabolism; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007116:Immunization, Passive; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D044045:Lipoxins; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009504:Neutrophils / Q000473:pathology; D019007:P-Selectin / Q000378:metabolism*; D011507:Proteinuria / Q000209:etiology
chemical_list: D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D019007:P-Selectin; C040527:lipoxin A4; D008084:Lipoxygenase