Leukocyte integrin expression in patients undergoing cardiopulmonary bypass.
BACKGROUND
The recruitment of leukocytes to vascular endothelium is controlled by adhesion events mediated through the beta2 integrins, whereas the response of extravasated leukocytes within the tissues is controlled through the beta1 integrins. Although cardiopulmonary bypass (CPB) has been shown to be associated with a systemic inflammatory response and elevated levels of beta2 integrins on leukocytes, its effect on the beta1 integrins is not known. This study investigated the effect of the protease inhibitor aprotinin on the expression of the beta1 and beta2 integrins on circulating leukocytes in patients undergoing CPB.


METHODS
Patients undergoing primary elective coronary artery bypass grafting were randomized into full-dose aprotinin or placebo groups. Blood samples were obtained at nine time points preoperatively, intraoperatively, and up to 6 days postoperatively. The surface expression of the beta1 integrins VLA-1, -3, -4, -5, and -6 and of the beta2 integrins CD11a/CD18, CD11b/CD18, and CD11c/CD18 was measured by flow cytometry on gated neutrophil and monocyte subpopulations in whole blood.


RESULTS
Expression of the beta1 integrins was not significantly altered during the study period and, therefore, aprotinin had no effect on the expression of these molecules. Of the beta2 integrins, CD11b/CD18 expression was significantly increased on neutrophils at 15 minutes after onset of CPB in the placebo group (p < 0.01) but not in the aprotinin group.


CONCLUSIONS
This study showed that expression of the beta1 integrins on neutrophils and monocytes did not alter during the first 6 days after CPB. Expression of the beta2 integrin CD11b/CD18 increased significantly on neutrophils during CPB in control patients but not in patients treated with full-dose aprotinin.
Asimakopoulos
G
G
National Heart and Lung Institute, Imperial College School of Medicine, London, England.
Kohn
A
A
Stefanou
D C
DC
Haskard
D O
DO
Landis
R C
RC
Taylor
K M
KM
D007611:Aprotinin / Q000627:therapeutic use*; D018821:CD18 Antigens / Q000378:metabolism*; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
D018821:CD18 Antigens; D019012:Integrin beta1; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin