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Thromb Haemost 1993; 70(05): 800-806
DOI: 10.1055/s-0038-1649673
Coagulation
Schattauer GmbH Stuttgart

Endotoxin-Induced Tissue Factor in Human Monocytes is Dependent upon Protein Kinase C Activation

C Ternisien
Service d'Hématologie et d'lmmunologie and INSERM U 294, CHU X. Bichat, Paris, France
,
M Ramani
Service d'Hématologie et d'lmmunologie and INSERM U 294, CHU X. Bichat, Paris, France
,
V Ollivier
Service d'Hématologie et d'lmmunologie and INSERM U 294, CHU X. Bichat, Paris, France
,
F Khechai
Service d'Hématologie et d'lmmunologie and INSERM U 294, CHU X. Bichat, Paris, France
,
T Vu
Service d'Hématologie et d'lmmunologie and INSERM U 294, CHU X. Bichat, Paris, France
,
J Hakim
Service d'Hématologie et d'lmmunologie and INSERM U 294, CHU X. Bichat, Paris, France
,
D de Prost
Service d'Hématologie et d'lmmunologie and INSERM U 294, CHU X. Bichat, Paris, France
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Publication History

Received 24 February 1993

Accepted after revision 02 June 1993

Publication Date:
05 July 2018 (online)

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Summary

Tissue factor (TF) is a transmembrane receptor which, in association with factors VII and Vila, activates factor IX and X, thereby activating the coagulation protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes transcribe, synthesize and express TF on their surface. We investigated whether LPS-induced TF in human monocytes is mediated by protein kinase C (PKC) activation. The PKC agonists phorbol 12- myristate 13-acetate (PMA) and phorbol 12, 13 dibutyrate (PdBu) were both potent inducers of TF in human monocytes, whereas 4 alpha-12, 13 didecanoate (4 a-Pdd) had no such effect. Both LPS- and PMA-induced TF activity were inhibited, in a concentration dependent manner, by three different PKC inhibitors: H7, staurosporine and calphostin C. TF antigen determination confirmed that LPS-induced cell-surface TF protein levels decreased in parallel to TF functional activity under staurosporine treatment. Moreover, Northern blot analysis of total RNA from LPS- or PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to H7 and staurosporine. The decay rate of LPS-induced TF mRNA evaluated after the arrest of transcription by actinomycin D was not affected by the addition of staurosporine, suggesting that its inhibitory effect occurred at a transcriptional level. We conclude that LPS-induced production of TF and its mRNA by human monocytes are dependent on PKC activation.

 

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