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 following physiological conditions: at 37 degrees 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 microg/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 A(2) 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.
Li
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N
Department of Medicine, Division of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
Hu
H
H
Lindqvist
M
M
Wikström-Jonsson
E
E
Goodall
A H
AH
Hjemdahl
P
P
D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D001800:Blood Specimen Collection; D002450:Cell Communication; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects; D019007:P-Selectin / Q000032:analysis / Q000096:biosynthesis; D015539:Platelet Activation; D013482:Superoxide Dismutase / Q000494:pharmacology
D016177:Macrophage-1 Antigen; D019007:P-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003094:Collagen; D013482:Superoxide Dismutase