Hydroxyl radical-mediated commitment of HL-60 cells to differentiation: Modulation of differentiation process by phosphodiesterase inhibitors.
- Author:
Jin Young CHO
1
;
Woong Shick AHN
;
Seok Ho CHA
;
Kweon Haeng LEE
;
Won Il KIM
;
Myung Hee CHUNG
Author Information
1. Dep. Pharmacol., Catholic Univ. Med. College, 505 Banpo-dong, Seocho-gu, Seoul 137-701 South Korea.
- Publication Type:Original Article
- MeSH:
1-Methyl-3-isobutylxanthine;
Acetylcysteine;
Adenosine;
Calcium;
Deferoxamine;
Dipyridamole;
HL-60 Cells*;
Humans;
Hydroxyl Radical;
Phosphodiesterase Inhibitors*;
Superoxides
- From:The Korean Journal of Physiology and Pharmacology
1998;2(3):369-376
- CountryRepublic of Korea
- Language:English
-
Abstract:
Ms report shows that hydroxyl radical, generated by a Fenton reaction involving adenosine 5'-diphosphate/Fe2+ complex (5-15 micrometer) and H2O2 (2 micrometer), induced differentiation of HL-60 cells in a dose- and time-dependent manner. This is evidenced by the increases in 12-O-tetradecanoylphorbol 13-acetate- and fMLP-stimulated superoxide production capability. The cells exposed to hydroxyl radical for defined periods (24~96 hr) continued to differentiate even after the hydroxyl radical generating system had been removed. The differentiated cells displayed fMLP-stimulated calcium mobilization and increased expression of myeloid-specific antigen CD11b and CD14. The extent of the differentiation was markedly reduced by desferrioxamine (100micrometer), dimethylthiourea (5 mM), N,N'-diphenyl-1,4-phenylenediamine (2 micrometer), and N-acetyl-L-cysteine (5 mM). The induction of differentiation by hydroxyl radical was enhanced by 3-isobutyl-1-methylxanthine (200 micrometer) and Ro-20-1724 (8 micrometer), and inhibited by dipyridamole (2 micrometer). These results suggest that hydroxyl radicals may induce commitment of HL-60 cells to differentiate into more mature cells of myelomonocytic lineage through specific signal-transduction pathway that is modulated by phosphodiesterase inhibitors.
