Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets

• Published in: Circulation (New York, N.Y.) N.Y.), 1997-05, Vol.95 (10), p.2387-2394
• Main Authors: NEUMANN, F.-J, MARX, N, GAWAZ, M, BRAND, K, OTT, I, ROKITTA, C, STICHERLING, C, MEINL, C, MAY, A, SCHÖMIG, A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Biological and medical sciences; Blood Platelets - metabolism; Blood Platelets - physiology; Cardiology. Vascular system; Cell Adhesion; Coronary heart disease; Cytokines - metabolism; Female; Heart; Humans; Leukocytes - metabolism; Leukocytes - physiology; Male; Medical sciences; Middle Aged; Monocytes - metabolism; Monocytes - physiology; Myocardial Infarction - blood; Myocardial Infarction - therapy; NF-kappa B - physiology; Thrombin - pharmacology
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.95.10.2387

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. 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; P = .003). In vitro, thrombin-stimulated fixed platelets bound to neutrophils and monocytes. Within 2 hours, this resulted in increased mRNA for interleukin (IL),1 beta, IL-8, and monocyte chemoattractant protein (MCP)-1 in unfractionated leukocytes. After 4 hours, IL-1 beta 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-kappa B activation. Inhibition of binding by anti-P selectin antibodies reduced the effect of activated platelets on cytokine production. In patients with AMI, leukocyte-platelet adhesion is increased. Binding of activated platelets induces IL-1 beta, IL-8, and MCP-1 in leukocytes. Our findings suggest that leukocyte-platelet adhesion contributes to the regulation of inflammatory responses in AMI.