Glomerular interleukin 1 production is dependent on macrophage infiltration in anti-GBM glomerulonephritis.
Both macrophages and glomerular mesangial cells have the potential to synthesize interleukin 1 (IL-1), however, their respective contributions to IL-1 production in anti-GBM glomerulonephritis (GN) are unknown. To address this problem, IL-1 production by glomeruli from rabbits with macrophage-associated anti-GBM GN (passive autologous anti-GBM GN [PAGBMGN]) and macrophage independent (heterologous phase) anti-GBM GN was studied. Macrophage-infiltrated nephritic glomeruli produced IL-1 bioactivity which was inhibitable by an anti-IL-1 antibody, and had a molecular weight consistent with rabbit IL-1. Glomerular IL-1 production in PAGBMGN was markedly augmented (1.43 +/- 0.79 U/10(3) glomeruli [gloms]/24 hr) compared to normal glomeruli (0.13 +/- 0.06 U/10(3) gloms/24 hr, P less than 0.05) or glomeruli from rabbits with macrophage independent GN (0.11 +/- 0.07 U/10(3) gloms/24 hr, P less than 0.05). IL-1 production by glomeruli from leukocyte depleted rabbits with PAGBMGN (0.16 +/- 0.07 U/10(3) gloms/24 hr) was not significantly elevated compared to normal glomeruli. Glomerular macrophages from rabbits with PAGBMGN produced more IL-1 (3.62 +/- 1.63 U/10(3) cells/24 hr) than blood monocytes (0.51 +/- 0.30 U/10(3) cells/24 hr) or alveolar macrophages (0.24 +/- 0.12 U/10(3) cells/24 hr) from the same animals. These results show that in experimental anti-GBM GN where injury is macrophage dependent, IL-1 production is also macrophage dependent and infiltrating glomerular macrophages are the major source of IL-1. Further, as glomerular IL-1 production was not significantly augmented in GN in the absence of macrophages, glomerular deposition of immunoglobulin and complement alone do not stimulate significant IL-1 production by intrinsic glomerular cells in experimental anti-GBM GN.
Tipping
P G
PG
Department of Medicine, Monash University, Prince Henry's Hospital, Melbourne, Australia.
Lowe
M G
MG
Holdsworth
S R
SR
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001323:Autoantibodies; D005921:Glomerulonephritis / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D011817:Rabbits
D000906:Antibodies; D001323:Autoantibodies; D007375:Interleukin-1; C051951:antiglomerular basement membrane antibody