Monocyte chemoattractant protein-1 expression correlates with monocyte infiltration in the post-ischemic kidney

Ren Fail. 2002 Nov;24(6):703-23. doi: 10.1081/jdi-120015673.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / immunology*
  • Acute Kidney Injury / urine
  • Animals
  • Biomarkers / urine
  • Chemokine CCL2 / genetics*
  • Chemokine CCL2 / pharmacokinetics
  • Chemokine CCL2 / urine*
  • Disease Models, Animal
  • Gene Expression / genetics*
  • Gene Expression / immunology*
  • Male
  • Neutrophil Infiltration / genetics*
  • Neutrophil Infiltration / immunology*
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics*
  • RNA, Messenger / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / immunology*
  • Reperfusion Injury / urine
  • Severity of Illness Index
  • Time Factors

Substances

  • Biomarkers
  • Chemokine CCL2
  • RNA, Messenger