Monocyte chemoattractant protein-1 mediates monocyte/macrophage influx in anti-thymocyte antibody-induced glomerulonephritis.
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.
Wenzel
U
U
Department of Medicine, University of Hamburg, Germany.
Schneider
A
A
Valente
A J
AJ
Abboud
H E
HE
Thaiss
F
F
Helmchen
U M
UM
Stahl
R A
RA
D000818:Animals; D000906:Antibodies; D000961:Antilymphocyte Serum / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D005921:Glomerulonephritis / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000473:pathology* / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000473:pathology* / Q000502:physiology*; D009500:Neutralization Tests; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D000961:Antilymphocyte Serum; D018932:Chemokine CCL2