Effect of leukocyte stimulation on rabbit immune complex glomerulonephritis.
Phytohemagglutinin (PHA), a leukocyte mitogen, induces a lymphocyte and blast cell glomerulonephritis in rat renal allografts (Cell Immunol 13:146, 1974). The aim of this study was to assess whether PHA similarly enhances rabbit monocyte-dependent experimental, acute immune complex glomerulonephritis, and whether this effect is associated with local release of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Rabbits with experimental acute serum sickness (AcSS: Group I) had focal proliferative and exudative glomerulonephritis with immune deposits, scattered subepithelial electron-dense deposits (humps), mild and transient proteinuria, normal creatinine clearance and slightly increased production of IL-1 and TNF from isolated glomeruli. Rabbits with AcSS and injected with PHA (Group II) developed severe lymphocyte and blast cell glomerulonephritis with diffuse endothelial damage; immune deposits were significantly reduced, focal subepithelial electron-dense deposits were absent, proteinuria was increased, creatinine clearance was decreased and production of IL-1 and TNF was markedly augmented as compared to rabbits in Group I. Rabbits with AcSS and injected with IL-1 beta and TNF alpha (Group V) had lesions comparable to those seen in Group II. These results show that PHA, IL-1 and TNF enhance the severity of acute immune complex glomerulonephritis, presumably by activating glomerular endothelial and mesangial cells and resident or infiltrated leukocytes.
Camussi
G
G
Dipartimento di Biochimica e Biofisica Università di Napoli, Italy.
Tetta
C
C
Bussolino
F
F
Turello
E
E
Brentjens
J
J
Montrucchio
G
G
Andres
G
G
D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology*; D007105:Immune Complex Diseases / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology*; D011817:Rabbits; D012713:Serum Sickness / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha