Chimeric 7E3 Fab (ReoPro) decreases detectable CD11b on neutrophils from patients undergoing coronary angioplasty

Objectives. The purpose of this study was to monitor the effects of chimeri c 7E3 Fab (ReoPro) on leukocyte and platelet activation and interaction dur ing coronary angioplasty. Background. Increased expression of CD11b on monocytes and neutrophils prom otes their adhesion to endothelial cells, extracellular matrix and smooth m uscle cells. Thrombin-activated platelets adhere via P-selectin to monocyte s and neutrophils. These cell interactions mag affect the outcome of corona ry angioplasty. Methods. During coronary angioplasty, venous blood was obtained for flow cy tometric detection of leukocyte CD11b; platelet CD41a, CD61a and CD62P; the percentage of leukocytes with adherent platelets and the intensity of boun d platelet fluorescence. Results. Leukocyte CD11b expression increased after angioplasty in control patients (neutrophils 171 +/- 25 to 255 +/- 31 mean fluorescence intensity [MFI, mean ct SEM], n = 25, p < 0.0001; monoecytes 200 +/- 40 to 248 +/- 36 MFI, n = 17, p < 0.05) and decreased in the patients selected to receive c himeric 7E3 Fab (neutrophils 146 +/- 30 to 82 +/- 22 MFI, n = 25, p < 0.000 1; monocytes 256 +/- 53 to 160 +/- 38 MFI, n 17, p < 0.05). Neutrophil CD11 b decreased after in vitro incubation of whole blood with chimeric 7E3 Fab (n = 5, p = 0.01), but fMLP-induced increases in CD11b were not prevented. The CD11b expression was unchanged and increased with fMLP stimulation afte r in vitro incubation of isolated neutrophils with chimeric 7E3 Fab. Direct -labeled chimeric 7E3 Fab was not detected bound to neutrophils in whole bl ood or isolated cells using bow cytometric techniques. Adhesion of isolated neutrophils to protein coated glass was not prevented by in vitro incubati on with chimeric 7E3 Fab. Platelet activation increased after angioplasty i n control patients (CD62P 8.9 +/- 0.8 to 12.3 +/- 1.2 MFI, n = 25, p < 0.05 ; CD41a 382 +/- 25 to 454 +/- 26 MFI, n = 25, p < 0.05, CD61a 436 +/- 52 to 529 +/- 58 MFI, n = 11, p < 0.05); it did not increase in the patients sel ected to receive chimeric 7E3 Fab (CD62P 13.2 +/- 1.0 to 9.0 +/- 0.9 MFI, n = 25, p < 0.05; CD61a 398 +/- 32 to 410 +/- 38 MFI, n = 7, p = NS). Leukoc ytes with adherent platelets tended to increase in the control group of pat ients and decrease after the procedure in patients selected to receive chim eric 7E3 Fab; individual and procedure-related variability were marked. Conclusions. Despite standard aspirin and heparin therapy, leukocyte and pl atelet activation with platelet adherence to leukocytes occurs after corona ry angioplasty. Although chimeric 7E3 Fab does not bind to leukocytes direc tly, it influences CD11b expression in whole blood. Modulation of platelet and leukocyte activation and interaction by chimeric 7E3 Fab may contribute to an improved outcome after coronary angioplasty. (C) 1998 by the America n College of Cardiology.