COLONY-STIMULATING FACTOR-I IN THE INDUCTION OF LUPUS NEPHRITIS

In this study we examine the role of colony stimulating factor-1 (CSF-1) in the induction of lupus nephritis. The purpose of the study was to establish the relationship of CSF-1 to the prominent influx of macrophages (Mphi) in the glomeruli of MRL-lpr mice with autoimmune lupus nephritis. The kidneys of MRL-lpr mice were examined before (< 12 weeks of age) and after (>12 weeks of age) renal injury for CSF-1 transcripts by in situ hybridization. CSF-1 mRNA was detected at four weeks of age within glomeruli and increased with disease severity. To examine whether glomerular Mphi (glom Mphi) required CSF-1 we isolated Mphi from the kidneys of MRL-lpr mice. Two types of glom Mphi (with morphological and growth characteristics which correlated with the presence or absence of proteinuria) were isolated. Under CSF-1-free culture conditions, where the viability of glom Mphi from proteinuric mice was maintained, glom Mphi from pre-proteinuric mice were unable to survive, Neutralization of CSF-1 in the media reduced viability of pre-proteinuric glom Mphi (5 to 6 X), while viability of proteinuric glom Mphi was diminished < 1,5 X. Additionally, CSF-1 supplementation induced a 10 x proliferation of pre-proteinuric glom Mphi when compared to CSF-1-free medium. In contrast, proteinuric glom Mphi did not proliferate in response to CSF-1. These studies suggest that CSF-1 induces macrophage proliferation and differentiation within glomeruli and, in turn, renal injury.