MONOCYTE CHEMOATTRACTANT PROTEIN-1 MEDIATES MONOCYTE MACROPHAGE INFLUX IN ANTI-THYMOCYTE ANTIBODY-INDUCED GLOMERULONEPHRITIS/

Chemokines are a family of chemotactic cytokines whose participation i n inflammation in vivo remains to be established. To study the role of monocyte-chemoattractant-protein-1 (MCP-1) on the glomerular accumula tion 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 gr anulocytes was analyzed by immunohistology. When studied by Northern b lotting, glomerular mRNA levels of MCP-1, and interleukin 1 beta (IL-1 beta) increased at three hours and 24 hours following the induction o f 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 an ti-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 af fect glomerular IL-1 beta, ICAM-1 or RANTES mRNA levels. The induction of glomerulonephritis was associated with an increased glomerular rec ruitment 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 4 0%, 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 glome rulonephritis. The reduction of M/M infiltration might affect this glo merular injury.