(Circulation. 1997;95:2387-2394.)
© 1997 American Heart Association, Inc.
Articles |
Induction of Cytokine Expression in Leukocytes by Binding of Thrombin-Stimulated Platelets
the Medizinische Klinik (F.-J.N., N.M., M.G., I.O., C.R., C.S., C.M., A.M., A.S.) and the Institut für Klinische Chemie and Pathobiochemie (K.B.) der Technischen Universität München, Munich, Germany.
Correspondence to Prof Dr Franz-Josef Neumann, 1 Medizinische Klinik der Technischen Universitä, Ismaninger Str 22, 81675 München, Germany. neumann{at}med1.med.tu-muenchen.de
Background Activated platelets tether and activate myeloid leukocytes. To investigate the potential relevance of this mechanism in acute myocardial infarction (AMI), we examined cytokine induction by leukocyte-platelet adhesion and the occurrence of leukocyte-platelet conjugates in patients with AMI.
Methods and Results We obtained peripheral venous blood samples in 20 patients with AMI before and daily for 5 days after direct percutaneous transluminal coronary angioplasty (PTCA) and in 20 patients undergoing elective PTCA. Throughout the study period, CD41 immunofluorescence of leukocytes (flow cytometry) revealed increased leukocyte-platelet adhesion in patients with AMI compared with control patients (mean±SE of fluorescence [channels] before PTCA: 77±16 versus 35±9; Pequals;.003). In vitro, thrombin-stimulated fixed platelets bound to neutrophils and monocytes. Within 2 hours, this resulted in increased mRNA for interleukin (IL)-1ß, IL-8, and monocyte chemoattractant protein (MCP)-1 in unfractionated leukocytes. After 4 hours, IL-1ß and IL-8 concentration of the cell-free supernatant had increased by 268±36% and 210±7%, respectively, and cellular MCP-1 content had increased by 170±8%. Addition of activated platelets to adherent monocytes had a similar effect and was associated with nuclear factor-
B activation. Inhibition of binding by anti–P-selectin antibodies reduced the effect of activated platelets on cytokine production.
Conclusions In patients with AMI, leukocyte-platelet adhesion is increased. Binding of activated platelets induces IL-1ß, IL-8, and MCP-1 in leukocytes. Our findings suggest that leukocyte-platelet adhesion contributes to the regulation of inflammatory responses in AMI.
Key Words: leukocytes • platelets • myocardial infarction
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