Hormonal control of lysosomal enzyme release from human neutrophils: elevation of cyclic nucleotide levels by autonomic neurohormones.
The influence of autonomic neurohormones on the immunologic release of beta-glucuronidase (EC 3.2.1.31) from, and the cyclic nucleotide levels in, human neutrophils was determined. Interaction of neutrophils with rheumatoid arthritic, serum-treated zymosan particles in a neutral balanced salt solution at 37 degrees resulted in the extracellular discharge of beta-glucuronidase without any loss of cell viability, as indicated by the failure of incubated cells to take up eosin Y or to release cytoplasmic lactate dehydrogenase (EC 1.1.1.27). Epinephrine reduced the release of beta-glucuronidase from neutrophils in the presence of zymosan during 2-30 min of incubation and elicited a concomitant elevation of adenosine 3':5'-monophosphate levels. Propranolol, a beta-adrenergic receptor antagonist, but not phentolamine, an alpha-adrenergic receptor antagonist, blocked both actions of epinephrine. Acetylcholine stimulated the release of beta-glucuronidase, but not lactate dehydrogenase, and provoked a concomitant elevation of guanosine 3':5'-monophosphate levels. Atropine, a muscarinic receptor antagonist, but not hexamethonium, a ganglionic blocker, inhibited both actions of acetylcholine. Interaction of neutrophils and zymosan particles resulted in an elevation of guanosine 3':5'-monophosphate levels within 2 min. These data suggest that intracellular guanosine 3':5'-monophosphate may be involved in mediating the immunologic release of lysosomal enzymes from human neutrophils whereas adenosine 3':5'-monophosphate may inhibit enzyme release. Moreover, autonomic neurohormones appear to be capable of modulating lysosomal enzyme release by virtue of their capacity to elevate neutrophil cyclic nucleotide levels.
D000109:Acetylcholine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D004336:Drug Antagonism; D004837:Epinephrine / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009504:Neutrophils / Q000201:enzymology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013268:Stimulation, Chemical; D013806:Theophylline / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D018377:Neurotransmitter Agents; D001285:Atropine; D015054:Zymosan; D011433:Propranolol; D013806:Theophylline; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; D006152:Cyclic GMP; D000109:Acetylcholine; D004837:Epinephrine; D010646:Phentolamine