Lack of albuminuria in the early heterologous phase of anti-GBM nephritis in beige mice.
Passive anti-glomerular basement membrane (GBM) nephritis in the mouse is accompanied by acute massive albuminuria in the early heterologous phase. As we have previously shown, this albuminuria does not occur in the beige mutant of the C57BL/6J strain which is deficient for the leukocytic neutral proteinases elastase and cathepsin G. To address the question whether an intrinsic defect in the polymorphonuclear granulocyte (PMN) or local factors in the beige kidney are responsible for the lack of albuminuria in the beige mouse strain, we conducted reciprocal bone marrow transplantations (BMT) in beige and congenic control mice. Injection of anti-GBM antibody resulted in only slight albuminuria (89 +/- 47 micrograms/18 hours; N = 6) in normal (that is, non-irradiated, non-reconstituted) beige mice. By contrast, in beige mice, reconstituted with bone marrow (BM) from control mice, acute albuminuria developed (3032 +/- 1408 micrograms/18 hours; N = 8), to a degree comparable to that in non-irradiated control mice (4411 +/- 3405 micrograms/18 hours; N = 6, P < 0.01). Albuminuria in control mice, reconstituted with beige BM, was in the range of the normal beige mice (112 +/- 55 micrograms/18 hours; N = 9). Reconstitution with syngeneic bone marrow demonstrated that BMT by itself did not influence the level of albuminuria. All mice showed similar morphological lesions, with comparable influx of PMN in the glomeruli two hours after antibody injection. Elastase activities of PMN extracts in BMT groups were not different from those in donor mice. We conclude that the absence of albuminuria in beige mice is caused by an intrinsic defect in leukocytic neutral proteinase activity.
Feith
G W
GW
Department of Pathology, University Hospital Nijmegen, The Netherlands.
Assmann
K J
KJ
Bogman
M J
MJ
van Gompel
A P
AP
Schalkwijk
J
J
Koene
R A
RA
D000419:Albuminuria / Q000209:etiology*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001485:Basement Membrane / Q000276:immunology; D016026:Bone Marrow Transplantation; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D004195:Disease Models, Animal; D007678:Kidney Glomerulus / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009393:Nephritis / Q000209:etiology* / Q000276:immunology; D009504:Neutrophils / Q000502:physiology; D010196:Pancreatic Elastase / Q000378:metabolism; D012697:Serine Endopeptidases
D000906:Antibodies; D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; C534096:Ctsg protein, mouse; D010196:Pancreatic Elastase