Initiation and evolution of interstitial leukocytic infiltration in experimental glomerulonephritis.
Most forms of glomerulonephritis have a significant interstitial leukocytic infiltrate which is associated with disease progression. However, there is little data concerning the timing, initial location, and development of this interstitial component. Therefore, we have addressed these issues in a study of passive accelerated anti-GBM glomerulonephritis in the rat. In this model, interstitial leukocytic infiltration was an early event in the disease process with a significant infiltrate apparent at 12 hours after administration of nephrotoxic serum (NTS). This initial infiltrate was restricted to a perivascular sheath surrounding the hilar arterioles. The sheath infiltrate then spread to include the whole hilar area by day 1, the entire periglomerular area by day 3, and became widespread throughout the cortical tubulointerstitium by day 7. The early sheath infiltrate was composed of macrophages and T cells. Both cell types continued to increase as the infiltrate expanded, and a significant accumulation of activated cells (IL-2R+) was evident from day 7 onwards. There was a highly significant correlation between interstitial macrophage infiltration and renal function impairment, proteinuria, and histologic damage. Interstitial T cell infiltration correlated with proteinuria and histologic damage, while the appearance of immune-activated mononuclear cells (IL-2R+) exhibited a highly significant correlation with all disease parameters. This study demonstrates the importance of the glomerular hilar arteriolar region as a focus for mononuclear leucocytic migration and accumulation which not only affects the structure and function of the glomerulus but subsequently the entire tubulointerstitium.
Lan
H Y
HY
Department of Nephrology, Monash Medical Centre, Prince Henry's Hospital, Melbourne, Victoria, Australia.
Paterson
D J
DJ
Atkins
R C
RC
D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D005921:Glomerulonephritis / Q000150:complications / Q000276:immunology / Q000473:pathology*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000032:analysis; D007249:Inflammation; D007678:Kidney Glomerulus / Q000276:immunology; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains
D007074:Immunoglobulin G