Platelet-leukocyte aggregation under shear stress: Differential involvement of selectins and integrins

Hu Hu; David Varon; Paul Hjemdahl; Naphtali Savion; Sam Schulman; Nailin Li

doi:10.1160/TH03-05-0274

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(04): 679-687
DOI: 10.1160/TH03-05-0274

Platelets and Blood Cells

Schattauer GmbH

Platelet-leukocyte aggregation under shear stress: Differential involvement of selectins and integrins

Hu Hu

¹Department of Medicine, Divisions of Clinical Pharmacology

,

David Varon

²Department of Hematology, Hadassah-Hebrew University Medical Centers, Jerusalem, Israel

,

Paul Hjemdahl

¹Department of Medicine, Divisions of Clinical Pharmacology

,

Naphtali Savion

³Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

,

Sam Schulman

⁴Department of Medicine, Divisions of Hematology, Karolinska Hospital, Stockholm, Sweden

,

Nailin Li

¹Department of Medicine, Divisions of Clinical Pharmacology

› Author Affiliations

Abstract

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.

Keywords

Platelets - leukocytes - platelet-leukocyte aggregate - shear stress - P-selectin - integrins

Full Text

References

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