© 2000 American Heart Association, Inc.
Thrombosis |
Platelet-Leukocyte Cross Talk in Whole Blood
From the Department of Medicine (N.L., H.H., M.L., E.W.-J., P.H.), Division of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden, and the Division of Chemical Pathology (A.H.G.), University of Leicester, Glenfield Hospital, Leicester, UK.
Correspondence to Paul Hjemdahl, MD, PhD, Professor, Department of Medicine, Division of Clinical Pharmacology, Karolinska Hospital, SE-171 76 Stockholm, Sweden. E-mail Paul.Hjemdahl{at}ks.se
Abstract—Thrombosis and inflammation involve complex platelet-leukocyte interaction, the details of which are not fully elucidated. Therefore, we investigated cross talk between platelets and leukocytes in whole blood, under the following physiological conditions: at 37°C, with normal calcium concentrations, and with shear force. Platelet P-selectin and leukocyte CD11b expression were used to monitor platelet and leukocyte activation, respectively, and platelet-leukocyte aggregation (PLA) was analyzed. The leukocyte-specific agonist N-formyl-methionyl-leucyl-phenylalanine (10-6 mol/L) increased P-selectin–positive platelets from 2.5±0.1% to 5.1±0.6% (P<0.05). The increase was inhibited by either the platelet-activating factor (PAF) antagonist SR27417, the superoxide anion scavenger superoxide dismutase, the 5-lipoxygenase inhibitor Zileuton, or the 5-lipoxygenase–activating protein inhibitor MK-886, suggesting the involvement of PAF, superoxide anion, and 5-lipoxygenase products in leukocyte-induced platelet activation. The platelet-specific agonist collagen (1 µg/mL) increased leukocyte CD11b expression from 2.94±0.52 to 3.81±0.58 (P<0.05); this was not inhibited by the thromboxane A2 receptor antagonist ICI 192.605 or the PAF antagonist SR27417. Platelet P-selectin expression induced by N-formyl-methionyl-leucyl-phenylalanine and leukocyte CD11b expression induced by collagen could be suppressed by glycoprotein IIb/IIIa blockade or P-selectin blockade. This study documents platelet-leukocyte cross talk under conditions that mimic a physiological state and suggests that this involves multiple mediators and mechanisms. Furthermore, new evidence of integrin and selectin involvement in intracellular and intercellular signaling during platelet-leukocyte cross talk is provided.
Key Words: platelets • leukocytes • platelet-leukocyte aggregates • platelet-leukocyte cross talk • whole blood
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