Pivotal role of colony stimulating factor-1 in lupus nephritis

Abstract

Spontaneous autoimmune renal injury in MRL-lpr mice shares many features of human lupus nephritis. We noted a prominent increase of macrophages (M phi) in the glomerulus of MRL-lpr mice. Since colony stimulating factor-1 (CSF-1) regulates M phi growth and is a potent chemoattractant, we explored the possibility that there was an increase in CSF-1 in MRL-lpr mice. We detected a biphasic increase in circulating CSF-1 in MRL-lpr mice as compared to congenic MRL- ++ mice other strains with the lpr gene, and normal mice. There was an increase in CSF-1 steady state mRNA transcripts in the kidney but not in the liver, lung or bone marrow. By in situ hybridization our studies identified the glomeruli as the predominant source of renal CSF-1. Enhanced CSF-1 is expressed by the mesangial cells at the same time (4 weeks of age) that M phi begin to accumulate in the glomeruli, well in advance of the loss of renal function. We have isolated pure populations of glomerular M phi in culture from MRL-lpr mice. These glomerular M phi require CSF-1 to survive and proliferate. Therefore, these data suggest that CSF-1 is increased in the glomerulus prior to the influx and accumulation of M phi. We propose that CSF-1 expression in the kidney is pivotal in the attraction and accumulation of M phi and in turn responsible for initiating tissue destruction.