Antibody to Intercellular Adhesion Molecule 1 Protects the Kidney Against Ischemic Injury

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-01, Vol.91 (2), p.812-816
• Main Authors: Kelly, K. J., Williams, Winfred W., Colvin, Robert B., Bonventre, Joseph V.
• Format: Article
• Language: English
• Subjects: Acute kidney failure; Acute Kidney Injury - etiology; Acute Kidney Injury - physiopathology; Acute Kidney Injury - prevention & control; Animals; Antibodies; Antibodies, Monoclonal - pharmacology; Biological and medical sciences; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - physiology; Creatinine - blood; Human resources; Immunity (Disease); Intercellular Adhesion Molecule-1; Ischemia; Ischemia - etiology; Ischemia - physiopathology; Ischemia - prevention & control; Kidney - blood supply; Kidney - pathology; Kidney - physiopathology; Kidney failure; Kidneys; Leukocytes; Lymphocyte Function-Associated Antigen-1 - immunology; Lymphocyte Function-Associated Antigen-1 - physiology; Male; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Peroxidase - metabolism; Physical trauma; Rats; Rats, Sprague-Dawley; Renovascular diseases; Reperfusion; Rodents; Time Factors; Vehicles
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.2.812

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.