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 (Mø) 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 Mø (glom Mø) required CSF-1 we isolated Mø from the kidneys of MRL-lpr mice. Two types of glom Mø (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 Mø from proteinuric mice was maintained, glom Mø from pre-proteinuric mice were unable to survive. Neutralization of CSF-1 in the media reduced viability of pre-proteinuric glom Mø (5 to 6 ×), while viability of proteinuric glom Mø was diminished < 1.5 ×. Additionally, CSF-1 supplementation induced a 10 × proliferation of pre-proteinuric glom Mø when compared to CSF-1-free medium. In contrast, proteinuric glom Mø 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.
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