Effect of glycoprotein IIb/IIIa antagonist abciximab on monocyte-platelet aggregates and tissue factor expression.
OBJECTIVE
Activated platelets rapidly adhere to monocytes and upregulate the expression of tissue factor (TF), the major trigger of the coagulation cascade. In this study, we examined the effect of abciximab, a nonselective glycoprotein IIb/IIIa-receptor antagonist, on monocyte TF expression in thrombin receptor activator-stimulated whole blood in vitro.


RESULTS
Abciximab (50 microg/mL) reduced the mass of platelets attached to monocytes, measured by the mean fluorescence intensity (MFI) of CD42b on CD14+ cells, 1 (CD42b, 471+/-197 versus 1073+/-217 MFI, mean+/-SD, P<0.05), 5, and 10 minutes after thrombin receptor activator stimulation of whole blood to the same extent as anti-P-selectin (50 microg/mL; 288+/-177 MFI, P<0.05) when determined by flow cytometry. In parallel, the expression of the platelet activation marker P-selectin colocalized with CD14+ monocytes was reduced up to 25% by abciximab at the same time points. Expression of monocyte TF antigen (CD14+/TF+, 39.9+/-8.7% versus 66.3+/-19.9%, P<0.05), chromogenic TF-activity (TF, 8.4+/-1.9 versus 13.2+/-2.8 U, arbitrary units, P<0.05), and TF mRNA was suppressed in the presence of abciximab as a consequence of reduced platelet mass attached to monocytes.


CONCLUSIONS
Our data suggest that heterotypic monocyte-platelet aggregates are a target for abciximab, which suppresses monocyte TF because of a reduction of monocyte-platelet cross talk.
Steiner
Sabine
S
Division of Angiology, University of Vienna, Austria.
Seidinger
Daniela
D
Huber
Kurt
K
Kaun
Christoph
C
Minar
Erich
E
Kopp
Christoph W
CW
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001792:Blood Platelets / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear; D008074:Lipoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010974:Platelet Aggregation / Q000276:immunology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000096:biosynthesis; D018179:Receptors, Thrombin / Q000276:immunology; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D008074:Lipoproteins; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012333:RNA, Messenger; D018179:Receptors, Thrombin; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D000077284:Abciximab