BACKGROUND: Chemokines are involved in the regulation of the cellular renal infiltrate in glomerulonephritis; however, it is unclear to which degree resident glomerular cells or infiltrating leukocytes contribute to the formation of chemokines in glomerular inflammatory lesions. We therefore examined whether monocytes/macrophages play a role in the expression of the C-C chemokines MCP-1/CCL2 and RANTES/CCL5 in renal tissue in a lipopolysaccharide (LPS)-induced model of inflammation, where previously we have shown increased glomerular RANTES expression and glomerular infiltration of ED-1-positive cells. METHODS: Inflammatory lesions were induced by an intraperitoneal injection of LPS. The infiltration of monocytes into the glomerulus was reduced by two experimental approaches. First, rats were depleted of monocytes by the use of specific monocyte-antisera or by cytotoxic drugs. Second, the infiltration of monocytes into the kidney was reduced by using intercellular adhesion molecule-1 (ICAM-1) knockout mice. RESULTS: Both experimental approaches demonstrated a significant reduction in the number of infiltrating monocytes/macrophages after lipopolysaccharide injection. This reduction in the infiltration of inflammatory cells was associated with significantly reduced RANTES/CCL5 mRNA expression. However, MCP-1/CCL2 mRNA expression was not inhibited after the LPS injection by monocyte/macrophage depletion. Also, the increase in nuclear factor-kappaB (NF-kappaB) binding activity after the LPS injection was not reduced in pretreated animals. The experiments therefore demonstrate that infiltrating monocytes/macrophages contribute to increased RANTES/CCL5 mRNA expression in inflammatory renal lesions, whereas MCP-1/CCL2 mRNA expression and NF-kappaB activation were not reduced by monocyte/macrophage depletion. CONCLUSION: MCP-1/CCL2 released from renal tissue upon stimulation plays a major role in the regulation of monocyte/macrophage infiltration, which contributes significantly to increased renal RANTES/CCL5 expression. This cross-talk between resident renal cells and monocytes/macrophages is therefore likely to boost the number of infiltrating inflammatory cells.
BACKGROUND: Chemokines are involved in the regulation of the cellular renal infiltrate in glomerulonephritis; however, it is unclear to which degree resident glomerular cells or infiltrating leukocytes contribute to the formation of chemokines in glomerular inflammatory lesions. We therefore examined whether monocytes/macrophages play a role in the expression of the C-C chemokines MCP-1/CCL2 and RANTES/CCL5 in renal tissue in a lipopolysaccharide (LPS)-induced model of inflammation, where previously we have shown increased glomerular RANTES expression and glomerular infiltration of ED-1-positive cells. METHODS: Inflammatory lesions were induced by an intraperitoneal injection of LPS. The infiltration of monocytes into the glomerulus was reduced by two experimental approaches. First, rats were depleted of monocytes by the use of specific monocyte-antisera or by cytotoxic drugs. Second, the infiltration of monocytes into the kidney was reduced by using intercellular adhesion molecule-1 (ICAM-1) knockout mice. RESULTS: Both experimental approaches demonstrated a significant reduction in the number of infiltrating monocytes/macrophages after lipopolysaccharide injection. This reduction in the infiltration of inflammatory cells was associated with significantly reduced RANTES/CCL5 mRNA expression. However, MCP-1/CCL2 mRNA expression was not inhibited after the LPS injection by monocyte/macrophage depletion. Also, the increase in nuclear factor-kappaB (NF-kappaB) binding activity after the LPS injection was not reduced in pretreated animals. The experiments therefore demonstrate that infiltrating monocytes/macrophages contribute to increased RANTES/CCL5 mRNA expression in inflammatory renal lesions, whereas MCP-1/CCL2 mRNA expression and NF-kappaB activation were not reduced by monocyte/macrophage depletion. CONCLUSION:MCP-1/CCL2 released from renal tissue upon stimulation plays a major role in the regulation of monocyte/macrophage infiltration, which contributes significantly to increased renal RANTES/CCL5 expression. This cross-talk between resident renal cells and monocytes/macrophages is therefore likely to boost the number of infiltrating inflammatory cells.
Authors: Teja Celhar; Richard Hopkins; Susannah I Thornhill; Raquel De Magalhaes; Sun-Hee Hwang; Hui-Yin Lee; Hiroko Yasuga; Leigh A Jones; Jose Casco; Bernett Lee; Thomas P Thamboo; Xin J Zhou; Michael Poidinger; John E Connolly; Edward K Wakeland; Anna-Marie Fairhurst Journal: Proc Natl Acad Sci U S A Date: 2015-10-28 Impact factor: 11.205
Authors: Phillipe D O'Brien; Junguk Hur; John M Hayes; Carey Backus; Stacey A Sakowski; Eva L Feldman Journal: Neurobiol Dis Date: 2014-10-30 Impact factor: 5.996
Authors: Mara L Lennard Richard; Shuzo Sato; Eiji Suzuki; Sarah Williams; Tamara K Nowling; Xian K Zhang Journal: J Immunol Date: 2014-08-06 Impact factor: 5.422
Authors: Nicolas Lerolle; Dominique Nochy; Emmanuel Guérot; Patrick Bruneval; Jean-Yves Fagon; Jean-Luc Diehl; Gary Hill Journal: Intensive Care Med Date: 2010-03 Impact factor: 17.440
Authors: Volha Ninichuk; Alexander G Khandoga; Stephan Segerer; Pius Loetscher; Achim Schlapbach; Laszlo Revesz; Roland Feifel; Andrej Khandoga; Fritz Krombach; Peter J Nelson; Detlef Schlöndorff; Hans-Joachim Anders Journal: Am J Pathol Date: 2007-04 Impact factor: 4.307
Authors: Xiang-Yang Zhu; Alejandro R Chade; James D Krier; Elena Daghini; Ronit Lavi; Angelo Guglielmotti; Amir Lerman; Lilach O Lerman Journal: J Hypertens Date: 2009-10 Impact factor: 4.844
Authors: Suzanne Av Van Asten; Adam Nichols; Javier La Fontaine; Kavita Bhavan; Edgar Jg Peters; Lawrence A Lavery Journal: Int Wound J Date: 2015-12-03 Impact factor: 3.315