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DOI: 10.1160/TH03-05-0274
Platelet-leukocyte aggregation under shear stress: Differential involvement of selectins and integrins
Financial support: The project was supported by the Swedish Research Council (5930), the Swedish Heart-Lung foundation, the Stockholm County Council, the Swedish Society of Medicine, and the Karolinska Institute.
Publication History
Received
08 May 2003
Accepted after revision
27 June 2003
Publication Date:
05 December 2017 (online)
Summary
Platelets and leukocytes can form heterotypic aggregates. We studied how shear stress influences platelet-leukocyte aggregation (PLA). Shear stress was applied to hirudinized blood, using a cone-and-plate(let) analyzer. Platelet and leukocyte activation and PLA formation were monitored by flow cytometry. Shear stress per se increased platelet P-selectin expression, leukocyte CD11b expression, and PLA formation. Shear-induced hetero-typic aggregation was seen among monocytes and neutrophils, but not lymphocytes. ADP induced marked PLA formation, but this was reduced by shear stress. fMLP mildly increased PLA formation, and this effect was enhanced by shear stress. P-selec-tin blockade abolished, whilst GPIIb/IIIa blockade enhanced shear- and agonist-induced PLA formation. At 1800 s-1, shear-and agonist-induced PLA formation were maintained or further enhanced with GPIIb/IIIa blockade alone, but reduced by simultaneous blockade of GPIIb/IIIa, CD11b, and CD18. In conclusion, shear stress per se enhances PLA formation. With agonist stimulation, shear stress enhances PLA formation primarily mediated by integrins, but attenuates PLA formation primarily mediated by P-selectin. The present results indicate that P-selectin-mediated bridging is essential for the initiation of PLA formation, while integrin-bridgings contribute importantly to the stability of heterotypic conjugates under high shear stress.
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