Platelet-leukocyte cross talk in whole blood

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 follo wing physiological conditions: at 37 degreesC, with normal calcium concentr ations, and with shear force. Platelet P-selectin and leukocyte CD11b expre ssion were used to monitor platelet and leukocyte activation, respectively, and platelet-leukocyte aggregation (PLA) was analyzed. The leukocyte-speci fic agonist N-formyl-methionyl-leucyl-phenylalanine (10(-6) mol/L) increase d 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) anta gonist SR27417, the superoxide anion scavenger superoxide dismutase, the 5- lipoxygenase inhibitor Zileuton, or the 5-lipoxygenase-activating protein i nhibitor MK-886, suggesting the involvement of PAF, superoxide anion, and 5 -lipoxygenase products in leukocyte-induced platelet activation. The platel et-specific agonist collagen (1 <mu>g/mL) increased leukocyte CD11b express ion from 2.94+/-0.52 to 3.81+/-0.58 (P<0.05); this was not inhibited by the thromboxane A,receptor antagonist ICI 192.605 or the PAF antagonist SR2741 7. Platelet P-selectin expression induced by N-formyl-methionyl-leucyl-phen ylalanine and leukocyte CD11b expression induced by collagen could be suppr essed by glycoprotein IIb/IIIa blockade or P-selectin blockade. This study documents platelet-leukocyte cross talk under conditions that mimic a physi ological state and suggests that this involves multiple mediators and mecha nisms. Furthermore, new evidence of integrin and selectin involvement in in tracellular and intercellular signaling during platelet-leukocyte cross tal k is provided.