MEDIATION OF IMMUNOLOGIC DISCHARGE OF LYSOSOMAL ENZYMES FROM HUMAN NEUTROPHILS BY GUANOSINE 3', 5r-MONOPHOSPHATE REQUIREMENT OF CALCIUM, AND INHIBITION BY ADENOSINE

The selective discharge of lysosome granule enzymes from human neutrophils by certain immunologic stimuli can be influenced in opposing directions by guanosine 3', 5'-monophosphate (cyclic GMP) 1 and adenosine 3', 5'-monophosphate (cyclic AMP) (1-3). Similarly, the immunologic secretion of lysosomal enzymes can be enhanced or inhibited by specific autonomic neurohormones (1-3). In fact, certain experimental evidence suggests that the enhancing action of acetylcholine and the inhibitory action of epinephrine on enzyme release from purified neutrophils may be mediated by intracellular cyclic GMP and cyclic AMP, respectively (4). Expression of the cellular actions of certain cholinergic and adrenergic agents by cyclic GMP and cyclic AMP, respectively, is well documented (5-10). Moreover, convincing evidence has been accumulated by Goldberg and co-workers (7, 8) that the opposing influences of cyclic GMP and cyclic AMP on various cellular processes provides the basis for the bidirectional regulation of cell function. The principal objective of the present investigation was to determine whether cyclic GMP plays a definitive role in mediating the immunologic discharge of lysosomal enzymes from human neutrophils. Recent reports from this laboratory indicated that cyclic GMP concentrations in neutrophils were elevated markedly during the lysosomal enzyme discharge that accompanied cell contact with serum-treated zymosan particles (4). In order to ascertain whether this direct relationship applies to all types of immunologic stimuli employed to provoke lysosomal enzyme release the neutrophil levels of cyclic GMP were moni-