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Thromb Haemost 1994; 72(04): 573-577
DOI: 10.1055/s-0038-1648917
Original Article
Schattauer GmbH Stuttgart

Thrombomodulin Induction by All-trans Retinoic Acid Is Independent of HL-60 Cells Differentiation to Neutrophilic Cells

Keiichiro Kizaki
The Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan
,
Hidemi Ishii
The Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan
,
Shuichi Horie
The Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan
,
Mutsuyoshi Kazama
The Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan
› Author Affiliations
Further Information

Publication History

Received 23 March 1994

Accepted after revision 08 June 1994

Publication Date:
06 July 2018 (online)

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Summary

The expression of thrombomodulin (TM), an antithrombotic factor, was investigated during neutrophilic differentiation of the HL-60 human myeloblastic cell line treated with d\\-trans retinoic acid (ATRA) or dimethyl sulfoxide (DMSO). Differentiation of the cells into neutrophilic cells progressed in a time- and dose-dependent fashion with ATRA or DMSO, as confirmed by the characteristic appearance of nitroblue tetrazolium (NBT) reduction and phagocytic activities, without induction of nonspecific esterase activity. TM antigen and cofactor activity for thrombin-dependent protein C activation were not detected in untreated HL-60 cells and the cells cultured with DMSO, but were expressed in a time-dependent manner in the cells cultured with ATRA. The level of TM expression in the HL-60 cells was not dose-dependent on ATRA concentrations, but maximum TM expression was obtained at 10−7 M ATRA. TM expression levels decreased in cells cultured with greater than 10−6 M ATRA, although the extent of cell differentiation into neutrophilic cells progressed at the higher ATRA concentrations. Since the TM antigen levels in the ATRA-treated cells also paralleled the TM mRNA levels, the data suggests that TM induction in the HL-60 cells cultured with ATRA reflected the levels of TM biosynthesis and was independent of HL-60 differentiation into neutrophilic cells. It was postulated that the appearance of TM with cofactor activity in neutrophilic cells differentiated from leukemic cells may contribute to prevention of vascular thrombosis in differentiation therapy of patients with acute promyelocytic leukemia by ATRA.

 

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