Inhibition of CD18-dependent leukocyte adherence by mAb 6.5 E does not prevent ischemia-reperfusion injury as seen in grafted kidneys.
The present study was designed to determine whether beta-2 integrin-mediated leukocyte adherence to the endothelium is involved in renal ischemia-reperfusion damage and to evaluate the therapeutic intervention potency of monoclonal antibody (mAb) 6.5 E, directed against the leukocyte CD18 adhesion molecule. To answer these questions, we used a clinically relevant canine model for the autotransplantation of kidneys that had been subjected to 30 min of normothermic ischemia, followed by 24 h of cold storage preservation. Intravital fluorescence microscopy of capsular microvessels showed that substantial leukocyte adherence occurred after renal ischemia and reperfusion. Leukocyte adherence was observed in both arterioles and venules, but predominantly in the latter. Reperfusion of the graft resulted in a statistically significant reduction of the venular red blood cell velocity (RBCV). Moreover, the venular diameter increased. No significant changes in the arteriolar RBCV or in the arteriolar diameter were observed. Administration of mAb 6.5 E, 1 h before reperfusion, inhibited leukocyte adherence to the renal microvascular endothelium, resulting in an improved venular flow 2 h after reperfusion. However, we observed no beneficial effect of mAb 6.5 E pretreatment on post-transplant graft function and survival. We conclude that leukocyte adherence does not play a critical role in the development of renal injury following reperfusion of kidneys that have been subjected to prolonged warm and cold ischemia.
Booster
M
M
Department of Surgery, University Hospital Maastricht, The Netherlands.
Yin
M
M
Kurvers
H A
HA
Tangelder
G J
GJ
Wijnen
R M
RM
Buurman
W A
WA
Heineman
E
E
Stubenitsky
B M
BM
Kootstra
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018821:CD18 Antigens / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects; D004285:Dogs; D005260:Female; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D015427:Reperfusion Injury / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens