CLINICAL STUDIES
Effect of glycoprotein IIb/IIIa receptor blockade on platelet-leukocyte interaction and surface expression of the leukocyte integrin Mac-1 in acute myocardial infarction
Franz-Josef Neumann, MDa,
Dietlind Zohlnhöfer, MDa,
Leila Fakhoury, MDa,
Ilka Ott, MDa,
Meinrad Gawaz, MDa and
Albert Schömig, MDa
a Deutsches Herzzentrum and 1. Medizinische Klinik der Technischen Universität München, Munich, Germany
Manuscript received January 14, 1999;
revised manuscript received May 20, 1999,
accepted June 28, 1999.
Reprint requests and correspondence: Dr. Franz-Josef Neumann, Deutsches Herzzentrum an der Technischen Universität, Lazarettstr. 36, 81636 München, Germany.
neumann{at}dhm.mhn.de
OBJECTIVES
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 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 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.
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Abbreviations and Acronyms
| | AMI | = acute myocardial infarction | | FITC | = fluoresceine isothiocyanate | | GP | = glycoprotein | | mAbs | = monoclonal antibodies | | PBS | = phosphate buffered saline | | PE | = phycoerythrine | | PSGL | = P-selectin glycoprotein ligand |
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