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Failure of F‐Met‐Leu‐Phe to Induce Chemotaxis in Differentiated Promyelocytic (HL‐60) Leukemia Cells
Author(s) -
Sirak Andrea A.,
Laskin Jeffrey D.,
Robertson Fredika M.,
Laskin Debra L.
Publication year - 1990
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.48.4.333
Subject(s) - biology , chemotaxis , acute promyelocytic leukemia , leukemia , cancer research , promyelocytic leukemia protein , microbiology and biotechnology , immunology , cell culture , genetics , retinoic acid , receptor
Treatment of HL‐60 promyelocytic leukemia cells with dibutyryl cyclic adenosine 3′,5′‐monophosphate (dbcAMP) induced these cells to differentiate toward mature neutrophilic granulocytes (PMN). DbcAMP was found to produce a rapid time‐ and dose‐dependent inhibition of HL‐60 cell proliferation, reaching a maximum after 48 hr treatment of the cells with 250–500 μM. This was associated with morphologic alterations consistent with maturing PMN. Using immunofluorescence and flow cytometry, we found that dbcAMP‐treated HL‐60 cells expressed some, but not all, surface markers characteristic of mature phagocytes. Thus receptors for the chemotactic peptide N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP); the monocyte/granulocyte markers My‐8, Mo‐1, and Leu‐15; as well as the monocyte markers Mo‐2 and My‐4 were identified on the cells. In contrast, dbcAMP‐treated cells did not express the PMN‐specific antigen DL1.2. We also found that dbcAMP‐treated HL‐60 cells produced hydrogen peroxide in response to the phorbol ester 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA). However, the magnitude of this response was significantly less than that observed in mature PMN. In contrast, fMLP‐stimulated levels of hydrogen peroxide production were comparable in both cell types. In addition, despite the fact that dbcAMP‐treated cells expressed fMLP receptors, they did not exhibit directed migration toward this chemotactic peptide. Taken together, these data suggest that dbcAMP‐induced differentiation of HL‐60 cells is incomplete.