Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury

Katherine Kelly, Winfred W. Williams, Robert B. Colvin, Shane M. Meehan, Timothy A. Springer, José Carlos Gutiérrez-Ramos, Joseph V. Bonventre

Research output: Contribution to journalArticle

601 Citations (Scopus)

Abstract

Studies in the rat have pointed to a role for intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of acute tubular necrosis. These studies used antibodies, which may have nonspecific effects. We report that renal ICAM-1 mRNA levels and systemic levels of the cytokines IL-1 and TNF- α increase 1 h after ischemia/reperfusion in the mouse. We sought direct proof for a critical role for ICAM-1 in the pathophysiology of ischemic renal failure using mutant mice genetically deficient in ICAM-1. ICAM-1 is undetectable in mutant mice in contrast with normal mice, in which ICAM-1 is prominent in the endothelium of the vasa recta. Mutant mice are protected from acute renal ischemic injury as judged by serum creatinine, renal histology, and animal survival. Renal leukocyte infiltration, quantitated morphologically and by measuring tissue myeloperoxidase, was markedly less in ICAM-1-deficient than control mice. To evaluate whether prevention of neutrophil infiltration could be responsible for the protection observed in the mutant mice, we treated normal mice with antineutrophil serum to reduce absolute neutrophil counts to <100 cells/mm3. These neutrophil-depleted animals were protected against ischemic renal failure. Anti-ICAM-1 antibody protected normal mice against renal ischemic injury but did not provide additional protection to neutrophil-depleted animals. Thus, ICAM-1 is a key mediator of ischemic acute renal failure likely acting via potentiation of neutrophil-endothelial interactions.

Original languageEnglish (US)
Pages (from-to)1056-1063
Number of pages8
JournalJournal of Clinical Investigation
Volume97
Issue number4
StatePublished - Feb 15 1996
Externally publishedYes

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Intercellular Adhesion Molecule-1
Kidney
Wounds and Injuries
Neutrophils
Acute Kidney Injury
Renal Insufficiency
Neutrophil Infiltration
Antibodies
Serum
Interleukin-1
Rectum
Peroxidase
Reperfusion
Endothelium
Creatinine
Histology
Leukocytes
Necrosis
Ischemia
Cytokines

Keywords

  • cell adhesion molecules
  • disease models, animal
  • endothelium, vascular
  • kidney failure, acute
  • leukocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kelly, K., Williams, W. W., Colvin, R. B., Meehan, S. M., Springer, T. A., Gutiérrez-Ramos, J. C., & Bonventre, J. V. (1996). Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury. Journal of Clinical Investigation, 97(4), 1056-1063.

Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury. / Kelly, Katherine; Williams, Winfred W.; Colvin, Robert B.; Meehan, Shane M.; Springer, Timothy A.; Gutiérrez-Ramos, José Carlos; Bonventre, Joseph V.

In: Journal of Clinical Investigation, Vol. 97, No. 4, 15.02.1996, p. 1056-1063.

Research output: Contribution to journalArticle

Kelly, K, Williams, WW, Colvin, RB, Meehan, SM, Springer, TA, Gutiérrez-Ramos, JC & Bonventre, JV 1996, 'Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury', Journal of Clinical Investigation, vol. 97, no. 4, pp. 1056-1063.
Kelly K, Williams WW, Colvin RB, Meehan SM, Springer TA, Gutiérrez-Ramos JC et al. Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury. Journal of Clinical Investigation. 1996 Feb 15;97(4):1056-1063.
Kelly, Katherine ; Williams, Winfred W. ; Colvin, Robert B. ; Meehan, Shane M. ; Springer, Timothy A. ; Gutiérrez-Ramos, José Carlos ; Bonventre, Joseph V. / Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury. In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 4. pp. 1056-1063.
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