Cytokine-induced neutrophil chemoattractant mediates neutrophil influx in immune complex glomerulonephritis in rat

Xiaobo Wu, Arthur J. Wittwer, Linda S. Carr, Barbara A. Crippes, Joseph E. DeLarco, James B. Lefkowith

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Chemokines are a family of cytokines whose participation in inflammation in vivo remains to be established. Using the rat model of anti-glomerular basement membrane (GBM) nephritis, we found that mRNA for the chemokine CINC (cytokine-induced neutrophil chemoattractant) was induced in the kidney, and the corresponding protein was elaborated by isolated inflamed glomeruli. Production of CINC by glomeruli was unaffected by complement- or leukocyte- depletion prior to disease induction. Cytokines which induce CINC expression in renal cells (TNF-α and IL-1β) were also expressed in the kidney during glomerular inflammation. TNF-α production, unlike CINC, was complement and leukocyte dependent. In vivo administration of anti-CINC, but not anti-human IL-8, IgG selectively attenuated the influx of PMNs into the glomerulus and commensurately diminished proteinuria. The participation of CINC was not tissue-specific: anti-CINC IgG also diminished the influx of PMNs in dermal immune complex inflammation. In sum, we propose that glomerular immune complex deposition/complement activation leads to cytokine production which results in CINC expression by endogenous glomerular cells. The CINC produced plays a contributory role in the influx of PMNs into the glomerulus in the context of the activation of other inflammatory mediators. These results suggest a potential role for CINC homologues, IL-8 and the GRO family of chemokines, in human immune complex-mediated disease.

Original languageEnglish
Pages (from-to)337-344
Number of pages8
JournalJournal of Clinical Investigation
Volume94
Issue number1
DOIs
StatePublished - Jul 1994

Keywords

  • CINC
  • IL-8
  • chemokine
  • immune complex
  • nephritis

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