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. 1974 May;71(5):2027–2031. doi: 10.1073/pnas.71.5.2027

Hormonal Control of Lysosomal Enzyme Release from Human Neutrophils: Elevation of Cyclic Nucleotide Levels by Autonomic Neurohormones

Louis J Ignarro 1, William J George 1
PMCID: PMC388378  PMID: 4151956

Abstract

The influence of autonomic neurohormones on the immunologic release of β-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° resulted in the extracellular discharge of β-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 β-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 β-adrenergic receptor antagonist, but not phentolamine, an α-adrenergic receptor antagonist, blocked both actions of epinephrine. Acetylcholine stimulated the release of β-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.

Keywords: guanosine 3′:5′-monophosphate, adenosine 3′:5′-monophosphate, lysosome membrane, acetylcholine, epinephrine

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Selected References

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