Effect of glycoprotein IIb/IIIa receptor blockade on platelet-leukocyte interaction and surface expression of the leukocyte integrin Mac-1 in acute myocardial infarction.
OBJECTIVE
This prospective randomized study investigated platelet-induced upregulation of Mac-1 on monocytes and its inhibition by glycoprotein (GP) IIb/IIIa blockage in patients with acute myocardial infarction (AMI).


BACKGROUND
In experimental AMI, Mac-1 on leukocytes is the pivotal adhesion molecule for detrimental inflammatory responses. In vitro, platelet adhesion to monocytes upregulates Mac-1.


METHODS
Patients undergoing stenting in AMI within 48 h after onset of symptoms were randomly assigned to receive either standard-dose heparin (n = 50) or abciximab plus low-dose heparin (n = 50). In serial blood samples, we assessed platelet-monocyte interaction and Mac-1 surface expression by triple color immunofluorescence flow cytometry.


RESULTS
Compared with platelet-negative monocytes, Mac-1 surface expression on monocytes with attached platelets was upregulated (median fluorescence intensity [interquartile range]: 259 [179 to 367] vs. 135 [78 to 195] arbitrary units, p < 0.001). As an indicator of platelet-monocyte interaction, mean fluorescence of the platelet marker GP Ib alpha in the monocytes population decreased after abciximab, although it remained unaffected by heparin alone. Abciximab achieved this effect by a reduction in platelet mass attached to monocytes (GP Ib alpha fluorescence intensity of heterotypic aggregates at 24 h [arbitrary units]: 187 [143 to 236] after abciximab vs. 228 [156 to 332] after heparin, p = 0.02), whereas it did not affect the percentage of monocytes with adherent platelets. Reduction of platelet-monocyte interaction resulted in decreased Mac-1 surface expression (fluorescence intensity at 24 h [arbitrary units]: 116 [68 to 153] after abciximab vs. 162 [117 to 239] after heparin, p = 0.001).


CONCLUSIONS
In patients with AMI, platelet-leukocyte interactions modulate Mac-1 expression on monocytes. Glycoprotein IIb/IIIa blockade is a therapeutic option to interfere with this mechanism.
Neumann
F J
FJ
Deutsches Herzzentrum and 1. Medizinische Klinik der Technischen Universität München, Munich, Germany. neumann@dhm.mhn.de
Zohlnhöfer
D
D
Fakhoury
L
L
Ott
I
I
Gawaz
M
M
Schömig
A
A
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001792:Blood Platelets / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007962:Leukocytes / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D015607:Stents; D015854:Up-Regulation / Q000502:physiology
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D016177:Macrophage-1 Antigen; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006493:Heparin; D000077284:Abciximab