Cytokine-induced neutrophil chemoattractant mediates neutrophil influx in immune complex glomerulonephritis in rat.
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-alpha and IL-1 beta) were also expressed in the kidney during glomerular inflammation. TNF-alpha 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.
Wu
X
X
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Wittwer
A J
AJ
Carr
L S
LS
Crippes
B A
BA
DeLarco
J E
JE
Lefkowith
J B
JB
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001483:Base Sequence; D002630:Chemotactic Factors / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D005921:Glomerulonephritis / Q000209:etiology*; D007074:Immunoglobulin G / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000502:physiology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000936:Antigen-Antibody Complex; D002630:Chemotactic Factors; D016207:Cytokines; D007074:Immunoglobulin G; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha