PMID: 9558118Apr 29, 1998Paper

IFN-gamma limits macrophage expansion in MRL-Fas(lpr) autoimmune interstitial nephritis: a negative regulatory pathway

The Journal of Immunology : Official Journal of the American Association of Immunologists
Andreas SchwartingV R Kelley

Abstract

IFN-gamma is capable of enhancing and limiting inflammation. Therefore, an increase in IFN-gamma in autoimmune MRL-Fas(lpr) mice could exacerbate or thwart renal injury. We have established a retroviral gene transfer approach to incite interstitial nephritis in MRL-Fas(lpr) mice that is rapid, enduring, and circumscribed. Renal tubular epithelial cells (TEC) were genetically modified to secrete macrophage (Mphi) growth factors (CSF-1-TEC, GM-CSF-1-TEC) and infused under the renal capsule. To determine the impact of IFN-gamma in Mphi growth factor-incited renal injury, we constructed a MRL-Fas(lpr) IFN-gamma-receptor (IFN-gammaR)-deficient strain. Gene transfer of CSF-1 or GM-CSF incited more severe interstitial nephritis in IFN-gammaR-deficient than in IFN-gammaR-intact MRL-Fas(lpr) mice, consisting of an increase of Mphi. To determine the mechanism responsible for the increase in Mphi in IFN-gammaR-deficient MRL-Fas(lpr) mice, we evaluated Mphi proliferation, apoptosis, and recruitment. Proliferation of bone marrow Mphi from IFN-gammaR-intact MRL-Fas(lpr) costimulated with CSF-1 or GM-CSF and IFN-gamma was reduced twofold, while the IFN-gammaR-deficient MRL-Fas(lpr) bone marrow Mphi remained stable. Furthermore, we detected mo...Continue Reading

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