CXCL10 induces the recruitment of monocyte-derived macrophages into kidney, which aggravate puromycin aminonucleoside nephrosis. (14th April 2015)

• Record Type: Journal Article
• Authors: Petrovic-Djergovic, D; Popovic, M; Chittiprol, S; Cortado, H; Ransom, R F; Partida-Sánchez, S
• Is Part Of: Clinical and experimental immunology. Volume 180:Number 2(2015:May)
• Page Start: 305
• Page End: 315
• Publication Date: 2015-04-14
• Subjects: chemokines -- CXCL10 -- kidney injury -- macrophages -- nephrotic syndrome; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12579
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: The mechanism responsible for trafficking of monocyte-derived macrophages into kidney in the puromycin aminonucleoside model of nephrotic syndrome in rats (PAN-NS), and the significance of this infiltration, remain largely unknown. CXCL10, a chemokine secreted in many T helper type 1 (Th1) inflammatory diseases, exhibits important roles in trafficking of monocytes and activated T cells. We hypothesized that induction of circulating interferon (IFN)-γ and glomerular tumour necrosis factor (TNF)-α during PAN-NS would stimulate the release of CXCL10 by podocytes, leading to infiltration of activated immune cells and greater glomerular injury. We found that serum IFN-γ, glomerular Cxcl10 mRNA and intra- and peri-glomerular macrophage infiltration were induced strongly during the late acute phase of PAN-NS in Wistar rats, but not in nude ( Foxn1 rnu/rnu ) rats lacking functional effector T lymphocytes. Wistar rats also developed significantly greater proteinuria than nude rats, which could be abolished by macrophage depletion. Stimulation of cultured podocytes with both IFN-γ and TNF-α markedly induced the expression of Cxcl10 mRNA and CXCL10 secretion. Together, these data support our hypothesis that increased circulating IFN-γ and glomerular TNF-α induce synergistically the production and secretion of CXCL10 by podocytes, attracting activated macrophages into kidney tissue. The study also suggests that IFN-γ, secreted from Th1 lymphocytes, may prime proinflammatory macrophages that consequently aggravate renal injury.