A CD18 monoclonal antibody reduces multiple organ injury in a model of ruptured abdominal aortic aneurysm.
The role of CD18 antibody (anti-CD18) in remote and local injury in a model of ruptured abdominal aortic aneurysm repair was investigated. Rats were divided into sham, shock, clamp, and shock + clamp groups. Shock + clamp animals received anti-CD18 or a control monoclonal antibody. One hour of hemorrhagic shock was followed by 45 min of supramesenteric aortic clamping. Intestinal and pulmonary permeability to (125)I-labeled albumin was determined. Myeloperoxidase (MPO) activity, F(2)-isoprostane levels, and transaminases were also measured. Only shock + clamp resulted in statistically significant increases in pulmonary and intestinal permeability, which were associated with significant increases in MPO activity and F(2)-isoprostane levels. Treatment with anti-CD18 significantly decreased intestinal and pulmonary permeability in shock + clamp animals. These reductions were associated with significantly reduced intestinal and hepatic MPO activity and pulmonary F(2)-isoprostane levels and reduced alanine and aspartate aminotransferase levels; however, anti-CD18 had no effect on intestinal or hepatic F(2)-isoprostane levels or on pulmonary MPO activity. These results suggest CD18-dependent and -independent mechanisms of local and remote organ injury in this model of ruptured abdominal aortic aneurysm.
Division of Vascular Surgery, Department of Surgery, The Toronto Hospital (General Division), Faculty of Medicine, University of Toronto, Toronto, Ontario M5C 2C4, Canada.
A J
AJ
Boyd
B B
BB
Rubin
P M
PM
Walker
A
A
Romaschin
T B
TB
Issekutz
T F
TF
Lindsay
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017544:Aortic Aneurysm, Abdominal / Q000150:complications*; D001019:Aortic Rupture / Q000150:complications*; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure; D016827:CD8 Antigens / Q000276:immunology*; D007422:Intestines / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000201:enzymology; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology* / Q000517:prevention & control*; D010539:Permeability; D009195:Peroxidase / Q000502:physiology; D011453:Prostaglandins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D011453:Prostaglandins; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase