N-acetyl-l-cysteine suppresses constitutive expression of CD11a/LFA-1α protein in myeloid lineage

Abstract 

We investigated the possible involvement of redox regulation in constitutive expression of CD11a/LFA-1α, a leukocyte integrin α subunit, in myeloid cells using antioxidants. In unstimulated HL-60 cells, CD11a/LFA-1α was highly expressed, however, no expression of CD11b and CD11c proteins was detected. N-acetyl-l-cysteine (NAC) markedly down-regulated CD11a/LFA-1α expression in a dose-dependent manner. The down-regulated CD11a/LFA-1α expression was gradually recovered when NAC was deprived 24h after treatment. Pyrrolidine dithiocarbamate (PDTC) also suppressed the level of expression CD11a/LFA-1α protein, although the effect of PDTC was less potent than NAC. Both NAC and PDTC suppressed NF-κB binding activity to consensus DNA probe, and this result was correlated with a suppressive effect to CD11a/LFA-1α expression. Furthermore, NAC also down-regulated CD11a/LFA-1α expression in both U937 cells and peripheral blood monocytes. These results indicated that the constitutive CD11a/LFA-1α 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.

Abbreviations:  LFA-1, lymphocyte-function-associated antigen 1, NAC, N-acetyl-l-cysteine, PDTC, pyrrolidine dithiocarbamate, ROS, reactive oxygen species, TPA, 12-O-tetradecanoyl phorbol-13-acetate, NF-κB, nuclear factor-kappa B

Keywords:  LFA-1, CD11a/LFA-1α, N-acetyl-l-cysteine, Pyrrolidine dithiocarbamate, Reactive oxygen species, Myeloid lineage