Participation of the interstitium in acute immune-complex nephritis: interstitial antigen accumulation, cellular infiltrate, and MHC class II expression.
Bovine serum albumin (BSA) injected into the rabbits induces acute immune complex glomerulonephritis. Since albumin is filtered and reabsorbed in the tubules, we investigated whether tubulointerstitial cells participate in the pathogenesis of this experimental condition. For this purpose, we induced immune-complex nephritis in 45 rabbits with the injection of 125I-BSA and urinary BSA excretion, glomerular and tubulointerstitial BSA accumulation, lymphocyte infiltration, proliferative activity and MHC class II antigens were examined 2, 4-5 and 6-8 days after immunization. Proteinuria developed day 6-8. BSA was found in urine from day 2 (mean +/- SE; 1089 +/- 339 micro g/24 h) and peaked on day 4 after immunization (2249 +/- 1106). BSA content (cpm/g tissue) in tubulointerstitium (TI) and glomeruli were similar at day 2 (457 +/- 45 and 407 +/- 75, respectively), but afterward increased significantly in TI, reaching a peak level on day 5 (1026 +/- 406) while remained unchanged in glomeruli (388 +/- 95). At the same time, preceding the onset of proteinuria, maximal intensity of the lymphocyte infiltration, proliferative activity and MHC class II antigen expression in tubular cells, monocytes/macrophages and interstitial cells were observed. Our study shows that antigen is excreted in the urine and concentrated in TI in association with overexpression of MHC class II molecules and lymphocyte infiltration. These findings occur prior to the development of proteinuria and suggest that the tubulointerstitial cells play a critical role in the pathogenesis of this model.
Parra
G
G
Centro de Medicina y Cirugía Experimental, Universidad del Zulia, Servicio de Nefrología, Hospital Universitario, Maracaibo, Venezuela. gus05121951@yahoo.com
Hernández
S
S
Moreno
P
P
Rodríguez-Iturbe
B
B
D000818:Animals; D000941:Antigens / Q000032:analysis* / Q000652:urine; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000652:urine; D007457:Iodine Radioisotopes; D007678:Kidney Glomerulus / Q000737:chemistry / Q000276:immunology; D007684:Kidney Tubules / Q000737:chemistry / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D011507:Proteinuria; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000032:analysis; D012713:Serum Sickness / Q000276:immunology*; D013997:Time Factors
D000941:Antigens; D000949:Histocompatibility Antigens Class II; D007457:Iodine Radioisotopes; D012710:Serum Albumin, Bovine