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Evidence for a selective inhibitory effect of thrombin on megakaryocyte progenitor growth mediated by the thrombin receptor
Author(s) -
Plantier JeanLuc,
Berthier Rolande,
Rival Yves,
Schweitzer Annie,
Rabiet MarieJosèphe
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb06735.x
Subject(s) - megakaryocyte , thrombin , thrombin receptor , receptor , progenitor cell , microbiology and biotechnology , protease activated receptor , monoclonal antibody , chemistry , agonist , biology , platelet , immunology , biochemistry , antibody , stem cell
Summary. An efficient method for the culture of human megakaryocyte precursors in serum‐free medium has been developed facilitating study of the effect of regulators of megakaryocyte growth and maturation without interference by serum‐derived factors. We have investigated how megakaryocytes and their precursors respond to the procoagulant enzyme, thrombin. In addition to its already documented agonist effect on mature megakaryocytes, thrombin was found to have a marked inhibitory effect on the growth of megakaryocyte colonies from CD34 + bone marrow cells stimulated by IL3. This inhibitory effect, not previously reported, was selective for megakaryocytic cells. The growth of granulomonocytic and erythroid colonies was not affected. A monoclonal antibody which neutralized the effect of exogenous transforming growth factor β (TGFβ) was unable to fully neutralize the inhibitory effect of thrombin. With the use of a synthetic peptide, corresponding to the tethered thrombin receptor ligand, and of a recombinant inactive form of thrombin, we provide direct evidence that both the inhibitory effect of thrombin on megakaryocyte proliferation and its agonist effect on mature magakaryocytes are mediated by a receptor analogous to the recently cloned platelet thrombin receptor.