Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury

K. J. Kelly, Winfred W. Williams, Robert B. Colvin, Joseph V. Bonventre

Research output: Contribution to journalArticlepeer-review

422 Scopus citations

Abstract

The pathophysiology of ischemic acute renal failure is complex, and the role of leukocyte adhesion in this process is not well defined. A monoclonal antibody (mAb) against intracellular adhesion molecule 1 (anti-ICAM-1), administered at the time of bilateral renal ischemia in the rat, prevented both functional impairment and histologic changes of acute renal failure. Plasma creatinine measured (mg/dl) 24 hr after 30 min of ischemia was 0.61 ± 0.05 in the anti-ICAM-1-treated animals compared with 2.4 ± 0.14 (P < 0.0001) in the vehicle-treated ischemic group. Forty-eight hours after ischemia, creatinine values were 0.46 ± 0.05 and 2.03 ± 0.22 (P < 0.0001) in anti-ICAM-1 and vehicle-treated groups, respectively. A low dose of anti- ICAM-1 that was itself nonprotective, when given with partially protective doses of a mAb against lymphocyte function-associated antigen-1 (anti-LFA- 1), acted synergistically to prevent renal failure. Anti-ICAM-1 mAb also protected the kidney when administered 0.5 or 2 hr but not 8 hr after restoration of blood flow and when the ischemic period was extended to 40 min. Ischemia-induced increases in tissue myeloperoxidase, a marker of neutrophil infiltration, were mitigated with anti-ICAM-1 treatment. Thus, anti-ICAM-1 mAb protected the kidney against ischemic renal failure, even when the antibody was administered after the ischemic period. These results suggest a critical role for leukocytes and adhesion molecules in the pathophysiology of ischemic injury and may have important therapeutic implications.

Original languageEnglish (US)
Pages (from-to)812-816
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number2
DOIs
StatePublished - Jan 18 1994

Keywords

  • acute renal failure
  • adhesion molecule receptors
  • integrins
  • ischemia-reperfusion injury

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury'. Together they form a unique fingerprint.

Cite this