Monocyte chemoattractant protein-1 mediates monocyte/macrophage influx in anti-thymocyte antibody-induced glomerulonephritis

• DOI: 10.1038/ki.1997.108
• Publication Date: 2007-05-08T15:33:32Z
• Authors: U. Wenzel; A. Schneider; A.J. Valente; Hanna E. Abboud; F. Thaiss; Udo M. Helmchen; Rolf A.K. Stahl
• Keywords: Male; Macrophages; Kidney Glomerulus; In Vitro Techniques; Antibodies; Monocytes; Rats; Chemotaxis, Leukocyte; 03 medical and health sciences; Glomerulonephritis; 0302 clinical medicine; Nephrology; Neutralization Tests; Animals; Rats, Wistar; Chemokine CCL2; Antilymphocyte Serum

Chemokines are a family of chemotactic cytokines whose participation in inflammation in vivo remains to be established. To study the role of monocyte-chemoattractant-protein-1 (MCP-1) on the glomerular accumulation of leukocytes, rats received a neutralizing anti-MCP-1 antiserum following the induction of an glomerulonephritis by an anti-thymocyte antibody (ATS). The infiltration of monocytes/macrophages (M/M) and granulocytes was analyzed by immunohistology. When studied by Northern blotting, glomerular mRNA levels of MCP-1, and interleukin 1 beta (IL-1 beta) increased at three hours and 24 hours following the induction of the injury. The glomerular mRNA expression of intercellular adhesion molecule-1 (ICAM-1) only increased marginally, whereas the expression of the chemokine RANTES was not enhanced. In animals that received anti-MCP-1 antibody glomerular MCP-1 mRNA expression increased. However, the chemoattractant activity for monocytes released into supernatants of isolated glomeruli was reduced. The anti-MCP-1 antibody did not affect glomerular IL-1 beta, ICAM-1 or RANTES mRNA levels. The induction of glomerulonephritis was associated with an increased glomerular recruitment of polymorphonuclear granulocytes (PMNs) at three hours and M/M at 24 hours, when compared with controls. The anti-MCP-1 antiserum significantly reduced the glomerular M/M infiltration at 24 hours by 40%, but was without effect on glomerular PMN recruitment or growth of the resident glomerular cells. These studies demonstrate that MCP-1 is an important mediator for monocyte recruitment in this model of glomerulonephritis. The reduction of M/M infiltration might affect this glomerular injury.