Chimeric 7e3 Fab (ReoPro) decreases detectable CD11b on neutrophils from patients undergoing coronary angioplasty
Judith K. Mickelson, MD, FACC*  ,
M. Nadir Ali, MD* ,
Neal S. Kleiman, MD, FACC*,
Nasser M. Lakkis, MD*,
Thomas W. Chow, PhD ,
Bonnie J. Hughes, BS and
C. Wayne Smith, MD
* Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030 USA
Speros P. Martel Laboratory of Leukocyte Biology, Department of Pediatrics, Baylor College of Medicine; Houston, Texas 77030 USA
Veterans Administration Medical Center, Houston, Texas, 77030 USA
Rice University, Houston, Texas, 77030, USA
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Figure 1 Leukocyte CD11b expression. Peripheral blood samples obtained pre- and postangioplasty were compared (paired t test). (a) Neutrophil CD11b expression in the control group increased (n = 25, p < 0.0001), while neutrophil CD11b expression decreased in the chimeric 7E3 group (n = 25, p < 0.0001). Postprocedure, neutrophil CD11b expression was lower in the chimeric 7E3 Fab group than the control group (p < 0.0001). (b) Monocyte CD11b expression in the control group increased (n = 17, p < 0.05), while monocyte CD11b expression decreased in the chimeric 7E3 group (n = 17, p < 0.05). Postprocedure, monocyte CD11b expression was lower in the chimeric 7E3 Fab group than in the control group (p < 0.05).
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Figure 2 Neutrophil CD11b expression. Peripheral blood samples obtained from healthy adult volunteers, incubated with 3.5 µg/ml chimeric 7E3 Fab at 37°C for 30 min, showed a decrease in each individual’s neutrophil CD11b expression (paired t test, n = 5). Peripheral whole blood samples obtained from healthy adult volunteers were incubated with 3.5 µg/ml chimeric 7E3 Fab at 37°C for 30 min and then stimulated with fMLP (10 nmol/liter) to determine if this apparent decrease in detectable CD11b was of functional significance. After stimulation, neutrophil CD11b expression increased dramatically regardless of the presence of chimeric 7E3 Fab (paired t test, n = 5). Two phycoerythrin-conjugated monoclonal antibodies were studied to confirm this finding (Leu-15, Becton Dickinson Immunocytometry Systems, San Jose, California; 2LPM19c, DAKOpatts, Denmark).
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Figure 3 Isolated neutrophil CD11b expression. Neutrophils isolated from peripheral blood of healthy adult volunteers were incubated with 3.5 µg/ml chimeric 7E3 Fab at 37°C for 30 min and then stimulated with fMLP (10 nmol/liter). There was no difference in CD11b expression with or without chimeric 7E3, either before or after stimulation with fMLP (paired t test, n = 5). Two phycoerythrin-conjugated monoclonal antibodies were studied to confirm this finding (Leu-15, Becton Dickinson Immunocytometry Systems, San Jose, California; 2LPM19c, DAKOpatts, Denmark).
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Figure 4 Platelet studies. Peripheral blood samples obtained pre- and postangioplasty were compared (paired t test). (a) Platelet P-selectin (CD62) expression in the control group increased (n = 25, p < 0.05), while platelet P-selectin (CD62) expression decreased in the chimeric 7E3 group (n = 25, p < 0.05). Preprocedure platelet P-selectin (CD62) expression was higher and postprocedure platelet P-selectin (CD62) expression was lower in the chimeric 7E3 Fab group than the control group (p < 0.01). (b) Platelet GP IIb/IIIa expression (as detected by anti-CD41a) in the control group increased (n = 25, p < 0.05), while the GP IIb/IIIa receptor was not accessible to the anti-CD41a in the chimeric 7E3 group (n = 25, p < 0.0001).
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