Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation

Mei Huei Jang, Deborah M. Herber, Xinnong Jiang, Sayan Nandi, Xu Ming Dai, Geraldine Zeller, E. Richard Stanley, Vicki R. Kelley

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

CSF-1, the major regulator of macrophage (Mφ) development, has three biologically active isoforms: a membrane-spanning, cell surface glycoprotein, a secreted glycoprotein, and a secreted proteoglycan. We hypothesized that there are shared and unique roles of individual CSF-1 isoforms during renal inflammation. To test this, we evaluated transgenic mice only expressing the cell surface or precursors of the secreted CSF-1 isoforms for Mφ accumulation, activation, and Mφ-mediated tubular epithelial cell (TEC) apoptosis during unilateral ureteral obstruction. The only difference between secreted proteoglycan and secreted glycoprotein CSF-1 isoforms is the presence (proteoglycan) or absence (glycoprotein) of an 18-kDa chondroitin sulfate glycosaminoglycan. We report that 1) cell surface CSF-1 isoform is sufficient to restore Mφ accumulation, activation, and TEC apoptosis to wild-type levels and is substantially more effective than the secreted CSF-1 isoforms; 2) the chondroitin sulfate glycosaminoglycan facilitates Mφ accumulation, activation, and TEC apoptosis; 3) increasing the level of secreted proteoglycan CSF-1 in serum amplifies renal inflammation; and 4) cell-cell contact is required for Mφ to up-regulate CSF-1-dependent expression of IFN-γ. Taken together, we have identified central roles for the cell surface CSF-1 and the chondroitin sulfate chain on secreted proteoglycan CSF-1 during renal inflammation.

Original languageEnglish (US)
Pages (from-to)4055-4063
Number of pages9
JournalJournal of Immunology
Volume177
Issue number6
DOIs
StatePublished - Sep 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Jang, M. H., Herber, D. M., Jiang, X., Nandi, S., Dai, X. M., Zeller, G., Stanley, E. R., & Kelley, V. R. (2006). Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation. Journal of Immunology, 177(6), 4055-4063. https://doi.org/10.4049/jimmunol.177.6.4055