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Inhibition by antimicrotubular agents of the procoagulant activity generated by the blood monocytes: A biochemical and morphological study
Author(s) -
de Prost Dominique,
Cramer Elisabeth,
Hakim Jacques
Publication year - 1979
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830060307
Subject(s) - colchicine , vinblastine , monocyte , incubation , in vitro , pharmacology , chemistry , cell , microbiology and biotechnology , biology , biochemistry , immunology , medicine , chemotherapy
During in vitro incubation, human blood leukocytes triggered by various stimuli, generate and release procoagulant activity (PCA), which was identified as tissue factor‐like activity. The cell responsible for this production is the monocyte. Monocytes, when incubated in aseptic conditions generate and release PCA in the incubation medium, after a lag period of 1–2 hours. Most of the activity (95%) remains cell bound while only 5% are released. In order to ascertain whether microtubules (MT) act as an intermediate in the generation and/or the release of PCA, monocytes were incubated with antimicrotubular agents ie, colchicine or vinblastine. Both drugs inhibited PCA generation and release. Colchicine added after two hours of incubation was inhibitor after a lag period of one hour as expected by its delayed effectiveness on MT. The inhibition was more effective on the generation than on the release of PCA. Ultrastructural studies showed that both drugs significantly (P < 0.01) disrupted microtubules while no modifications of the protein synthetizing apparatus or the lysosomes were observed. No accumulating material was seen inside the cells. These results suggest that colchicine or vinblastine act by their disrupting activity on MT, as inhibitors of PCA Generation by the monocytes. The decrease in PCA‐release would thus be secondary to a deficient generation of the activity. The absence of morphological modifications of the protein synthetizing apparatus suggest that antimicrotubular agents inhibit PCA synthesis by monocytes through the formation or transmission of the stimuli and not directly on the synthetizing sites.