Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury.
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.
Kelly
K J
KJ
Medical Service, Massachusetts General Hospital, Boston.
Williams
W W
WW
Colvin
R B
RB
Bonventre
J V
JV
D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D003404:Creatinine / Q000097:blood; D018799:Intercellular Adhesion Molecule-1; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D003404:Creatinine; D009195:Peroxidase