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

Kidney Int. 1997 Mar;51(3):770-6. doi: 10.1038/ki.1997.108.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Antilymphocyte Serum / pharmacology
  • Chemokine CCL2 / antagonists & inhibitors
  • Chemokine CCL2 / immunology
  • Chemokine CCL2 / physiology*
  • Chemotaxis, Leukocyte / physiology
  • Glomerulonephritis / etiology
  • Glomerulonephritis / pathology*
  • Glomerulonephritis / physiopathology*
  • In Vitro Techniques
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiopathology
  • Macrophages / pathology*
  • Macrophages / physiology*
  • Male
  • Monocytes / pathology*
  • Monocytes / physiology*
  • Neutralization Tests
  • Rats
  • Rats, Wistar

Substances

  • Antibodies
  • Antilymphocyte Serum
  • Chemokine CCL2