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


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; 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.


CONCLUSIONS
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.
Neumann
F J
FJ
Medizinische Klinik, Technischen Universität München, Germany. neumann@medl.med.tu-muenchen.de
Marx
N
N
Gawaz
M
M
Brand
K
K
Ott
I
I
Rokitta
C
C
Sticherling
C
C
Meinl
C
C
May
A
A
Schömig
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D009203:Myocardial Infarction / Q000097:blood* / Q000628:therapy; D016328:NF-kappa B / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology*
D016207:Cytokines; D016328:NF-kappa B; D013917:Thrombin