Neutralization of Gro alpha and macrophage inflammatory protein-2 attenuates renal ischemia/reperfusion injury

Am J Pathol. 2001 Dec;159(6):2137-45. doi: 10.1016/s0002-9440(10)63065-9.


Previous studies have provided strong evidence for a role for neutrophils in mediating pathology during reperfusion of ischemic tissues. CXC chemokines including interleukin-8, KC/Gro alpha, and macrophage inflammatory protein (MIP)-2, direct neutrophils to tissue sites of inflammation. In the current study we tested the efficacy of antibodies to KC/Gro alpha and MIP-2 in inhibiting neutrophil infiltration into kidneys during reperfusion after 1 hour of warm ischemia using a mouse model. KC mRNA and protein were produced within 3 hours after reperfusion of the ischemic kidneys. MIP-2 mRNA and protein were twofold to fourfold lower than KC and were at low levels until 9 hours after reperfusion. Only 60% of mice subjected to ischemia/reperfusion injury survived to day 3 after reperfusion. Treatment with rabbit neutralizing antibodies to both KC and MIP-2 inhibited neutrophil infiltration into ischemic kidneys during reperfusion, restored renal function as assessed by decreased serum creatinine and urea nitrogen levels to near normal levels, and resulted in complete survival of treated animals. Finally, treatment with both antibodies significantly reduced histologically graded pathology of kidneys subjected to ischemia/reperfusion injury. Collectively, the results indicate the efficacy of neutralizing the chemokines directing neutrophils into ischemic kidneys during reperfusion to inhibit this infiltration and attenuate the resulting pathology.

Publication types

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

MeSH terms

  • Animals
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines / genetics
  • Chemokines / immunology*
  • Chemokines / metabolism
  • Chemokines, CXC*
  • Chemotactic Factors / genetics
  • Chemotactic Factors / immunology*
  • Chemotactic Factors / metabolism
  • Gene Expression Regulation / drug effects
  • Growth Substances / genetics
  • Growth Substances / immunology*
  • Growth Substances / metabolism
  • Immune Sera / immunology
  • Immune Sera / pharmacology*
  • Intercellular Signaling Peptides and Proteins*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neutralization Tests
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Time Factors


  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, mouse
  • Cxcl2 protein, mouse
  • Growth Substances
  • Immune Sera
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger