Colony stimulating factor-1 in the induction of lupus nephritis

Kidney Int. 1993 May;43(5):1000-9. doi: 10.1038/ki.1993.141.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Cell Survival
  • Cells, Cultured
  • Kidney Glomerulus / pathology
  • Lupus Nephritis / genetics
  • Lupus Nephritis / metabolism*
  • Lupus Nephritis / pathology
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Macrophage Colony-Stimulating Factor / physiology
  • Macrophages / pathology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Mutant Strains
  • Phenotype
  • Proteinuria / genetics
  • Proteinuria / metabolism
  • Proteinuria / pathology
  • Tissue Distribution


  • Macrophage Colony-Stimulating Factor