Modulation of superoxide anion release from human polymorphonuclear cells by Met- and Leu-enkephalin

The present work describes the ability of Met- and Leu-enkephalin to modulate the superoxide anion (O2-) release from unstimulated human polymorphonuclear cells (PMN) and from PMN stimulated with phorbol myristate acetate (PMA). The direction (stimulation or suppression) and the magnitude of change were dependent upon the baseline reactivity of the donor's PMN. Both opioid peptides stimulated O2- release by PMN from donors with low baseline reactivity in a concentration-dependent manner. PMNs collected from donors with medium baseline reactivity incubated with Leu-enkephalin regardless of concentration released less O2- than control, nontreated PMNs. Met-enkephalin stimulated O2- release but only at 2 X 10(-15) M concentration. Superoxide anion release from PMNs of individuals with high baseline reactivity was concentration dependent and suppressed by Met- and Leu-enkephalin. Leu-enkephalin induced baseline reactivity was dependent upon progressive increase in the magnitude of change on O2- release (i.e., the higher the baseline the higher the magnitude of change in O2- generation). Met-enkephalin data show this also, but to a lesser extent. In cells stimulated with PMA, Met-enkephalin caused additional O2- release, while Leu-enkephalin was ineffective in triggering already stimulated cells. The modulating effect of both opioid peptides on superoxide anion release by human PMN is a short phenomenon that lasts up to 10 min after the addition of the peptide.