Colony stimulating factor-1 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 (M phi) 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 M phi (glom M phi) required CSF-1 we isolated M phi from the kidneys of MRL-lpr mice. Two types of glom M phi (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 M phi from proteinuric mice was maintained, glom M phi from pre-proteinuric mice were unable to survive. Neutralization of CSF-1 in the media reduced viability of pre-proteinuric glom M phi (5 to 6 x), while viability of proteinuric glom M phi was diminished < 1.5 x. Additionally, CSF-1 supplementation induced a 10 x proliferation of pre-proteinuric glom M phi when compared to CSF-1-free medium. In contrast, proteinuric glom M phi 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.
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
R D
RD
Bloom
S
S
Florquin
G G
GG
Singer
D C
DC
Brennan
V R
VR
Kelley
D000818:Animals; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D007678:Kidney Glomerulus / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000502:physiology; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D010641:Phenotype; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution
D016173:Macrophage Colony-Stimulating Factor