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Platelet-Derived Interleukin-1 Induces Cytokine Production, but not
Proliferation of Human Vascular Smooth Muscle Cells
Harald Loppnow,
Rosita Bil,
Stephan Hirt,
Uwe Schönbeck,
Mona Herzberg,
Karl Werdan,
Ernst Theodor Rietschel,
Ernst Brandt, and
Hans-Dieter Flad
From Forschungszentrum Borstel, Zentrum für Medizin und
Biowissenschaften, Borstel; Martin-Luther-Universität
Halle-Wittenberg, Halle/Saale; and Klinik für Herz und
Gefäß-Chirurgie der Christian-Albrechts-Universität zu
Kiel, Kiel, Germany.
During vascular injury, such as observed in atherosclerosis,
restenosis, vasculitides, transplantation, or sepsis, vascular smooth
muscle cells (SMC) can be exposed to platelets or platelet products.
Under these conditions proliferation or cytokine production of SMC
stimulated by platelets or platelet products may contribute to
regulation of vascular pathogenesis. Thus, we investigated interleukin-6 (IL-6) and IL-8 production as well as proliferation of
SMC in response to platelets or platelet lysates. Platelets not already
preactivated by thrombin induced IL-6 (10- to 50-fold) or IL-8
production of unstimulated SMC in a cell number dependent fashion.
Preactivation of platelets with thrombin potently increased the
platelet-mediated IL-6 (50- to 1,000-fold) and IL-8 production of SMC.
Hirudin specifically inhibited the activation of platelets with
thrombin. Isolated platelets cultured in the absence of SMC did not
contain detectable IL-6 or IL-8. Prestimulation (4 hours) of SMC with
pathophysiologically relevant substances
(lipopolysaccharide [LPS], tumor necrosis factor- [TNF- ], or
IL-1 ) further increased the platelet-induced cytokine production.
The platelet-derived SMC stimulatory activity was IL-1, since IL-1
receptor antagonist (IL-1-Ra) inhibited the platelet-induced cytokine
production of SMC. Anti-platelet-derived growth factor
(PDGF)-antibody did not further reduce this activity.
Thrombin itself stimulated expression of IL-6 and IL-8 to some degree
and induced IL-6 production of SMC synergistically with IL-1. Platelets
also induced proliferation of SMC, however, anti-PDGF antibodies,
rather than IL-1-Ra blocked this response. These data show that
platelet-derived IL-1 stimulates cytokine production of vascular smooth
muscle cells, indicating that platelet-derived IL-1 may contribute to
regulation of local pathogenesis in the vessel wall by activation of
the cytokine regulatory network.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 134-141
© 1998 by The American Society of Hematology.

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