Requirements for leukocyte adhesion molecules in nephrotoxic nephritis.
Requirements for leukocyte adhesion molecules as well as cytokines have been determined in the rat model of acute nephrotoxic nephritis. Proteinuria (at 24 h) and neutrophil accumulation in renal glomeruli (at 6 h) have been used as the endpoints. For full accumulation in glomeruli of neutrophils as well as full development of proteinuria, requirements have been demonstrated for TNF alpha, (but not IL-1), CD11b (but not CD11a), very late arising-4 (CD49d/CD29), and intercellular adhesion molecule-1 but not endothelial leukocyte adhesion molecule-1 (E-selectin). By immunohistochemical approaches, infusion of antibody to glomerular basement membrane induced glomerular upregulation of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular adhesion molecule-1. Treatment of rats with anti-TNF alpha or soluble recombinant human TNF receptor-1 blocked this expression. Renal arterial infusion of TNF alpha induced glomerular expression of all three endothelial adhesion molecules, but infusion of IL-1 beta did not. These data suggest that, in neutrophil and complement-dependent anti-glomerular basement membrane-induced acute nephritis in rats, there are selective requirements for cytokines, beta 1 and beta 2 integrins, and endothelial adhesion molecules. These requirements contrast with those found in other vascular beds in which complement and neutrophil-induced vascular injury has been induced by deposition of immune complexes.
Mulligan
M S
MS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Johnson
K J
KJ
Todd
R F
RF
Issekutz
T B
TB
Miyasaka
M
M
Tamatani
T
T
Smith
C W
CW
Anderson
D C
DC
Ward
P A
PA
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001485:Basement Membrane / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000502:physiology*; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000502:physiology; D007678:Kidney Glomerulus / Q000276:immunology; D009393:Nephritis / Q000209:etiology*; D009504:Neutrophils / Q000276:immunology; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1