N-acetyl-L-cysteine suppresses constitutive expression of CD11a/LFA-1alpha protein in myeloid lineage.
We investigated the possible involvement of redox regulation in constitutive expression of CD11a/LFA-1alpha, a leukocyte integrin alpha subunit, in myeloid cells using antioxidants. In unstimulated HL-60 cells, CD11a/LFA-1alpha was highly expressed, however, no expression of CD11b and CD11c proteins was detected. N-acetyl-L-cysteine (NAC) markedly down-regulated CD11a/LFA-1alpha expression in a dose-dependent manner. The down-regulated CD11a/LFA-1alpha expression was gradually recovered when NAC was deprived 24h after treatment. Pyrrolidine dithiocarbamate (PDTC) also suppressed the level of expression CD11a/LFA-1alpha protein, although the effect of PDTC was less potent than NAC. Both NAC and PDTC suppressed NF-kappaB binding activity to consensus DNA probe, and this result was correlated with a suppressive effect to CD11a/LFA-1alpha expression. Furthermore, NAC also down-regulated CD11a/LFA-1alpha expression in both U937 cells and peripheral blood monocytes. These results indicated that the constitutive CD11a/LFA-1alpha expression in the myeloid lineage is implicated in oxidative stress occurring spontaneously, suggesting that alteration of the intracellular redox state using antioxidants may be effective in the modulation of cell adhesion associated with extravasation in leukocytes, at least, in myeloid cells.
Hashizume
Kaoru
K
Department of Immunohistochemistry, DAKO Japan Company Ltd., Kakkyoyama 18, Nishinotoin-higashiiru, Shijo-dori, Simogyo, Kyoto, Japan.
Hatanaka
Yutaka
Y
Fukuda
Itsuko
I
Sano
Takashi
T
Yamaguchi
Yukihiro
Y
Tani
Yoichi
Y
Danno
Gen-ichi
G
Suzuki
Keiichiro
K
Ashida
Hitoshi
H
D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D019070:Cell Lineage; D015342:DNA Probes / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D022423:Myeloid Cells / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011485:Protein Binding / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D020298:U937 Cells
D000975:Antioxidants; D015342:DNA Probes; D016169:Lymphocyte Function-Associated Antigen-1; D016328:NF-kappa B; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D000111:Acetylcysteine