Monocyte chemoattractant protein-1 expression correlates with monocyte infiltration in the post-ischemic kidney.
Chemokines play a prominent role in the acute inflammatory response in several models of kidney disease. We reported that monocyte chemotactic peptide-1 (MCP-1) mRNA is increased by ischemia-reperfusion injury. In this report, we examined the effects of ischemia-reperfusion injury on the kinetics and location of MCP-1 protein expression, the excretion of MCP- 1 protein in the urine and on the infiltration of mononuclear cells in the kidney. Pair-fed Sprague-Dawley rats underwent bilateral renal ischemia (50 min) or sham ischemia and placed in metabolic cages for daily urine collections. Kidneys were harvested at d. 1, 3, 7, and 10 after ischemia-reperfusion (I-R) or sham-ischemia (S-I). Kidney MCP-1 mRNA levels were increased on d. I and 3 post-ischemia. Kidney MCP-1 protein levels were increased in the I-R group on d. 1 and 3. MCP-1 expression occurred predominantly in the distal tubule segments by immunohistology. There was an increase in monocytes/macrophages infiltration in the I-R group, compared to the S-I or controls by d. 1. Urinary MCP-1 excretion increased 3-fold in the I-R group, and remained elevated above the S-I group and baseline levels, on d. 3 through d. 8. Kidney MCP-1 mRNA levels, protein levels and urinary MCP-1 excretion rates are increased by ischemia-reperfusion injury. The areas of increase in MCP-1 chemoattractant expression correlates with an increase in monocyte infiltration in the kidney. Although its pathophysiologic role remains to be determined, MCP-1 may participate in, and be a biomarker for, the mononuclear inflammatory processes that occur after ischemia-induced acute renal failure.
Rice
James C
JC
Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-0562, USA. jrice@utmb.edu
Spence
Jeff S
JS
Yetman
Deborah L
DL
Safirstein
Robert L
RL
D058186:Acute Kidney Injury / Q000235:genetics* / Q000276:immunology* / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D018932:Chemokine CCL2 / Q000235:genetics* / Q000493:pharmacokinetics / Q000652:urine*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics* / Q000276:immunology*; D008297:Male; D020556:Neutrophil Infiltration / Q000235:genetics* / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics* / Q000276:immunology* / Q000652:urine; D012720:Severity of Illness Index; D013997:Time Factors
D015415:Biomarkers; D018932:Chemokine CCL2; D012333:RNA, Messenger