Acute passive anti-glomerular basement membrane nephritis in P-selectin-deficient mice.
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.
Mayadas
T N
TN
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Mendrick
D L
DL
Brady
H R
HR
Tang
T
T
Papayianni
A
A
Assmann
K J
KJ
Wagner
D D
DD
Hynes
R O
RO
Cotran
R S
RS
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
D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D019007:P-Selectin; C040527:lipoxin A4; D008084:Lipoxygenase