Bioregulation of lysosomal enzyme secretion from human neutrophils: roles of guanosine 3':5'-monophosphate and calcium in stimulus-secretion coupling.
Open Access
- 1 January 1975
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 72 (1), 108-112
- https://doi.org/10.1073/pnas.72.1.108
Abstract
The biologic role of calcium and guanosine 3':5'-monophosphate (cyclic GMP) in the immunologic secretion of lysosomal enzymes from human neutrophils was studied. Contact of neutrophils with zymosan-treated serum or the divalent cation ionophore A-23187, in the presence of extracellular calcium, resulted in beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase, EC 3.2.1.31) secretion and a concomitant accumulation of cyclic GMP without any loss of cell viability. Acetylcholine (0.1 muM), in the presence of calcium, enhanced the immunologic stimulation of cyclic GMP accumulation and lysosomal enzyme discharge. A marked and rapid association of 45CaCl2 with neutrophils occurred during cell surface contact with zymosan-treated serum, and this effect on calcium association was enhanced with 0.1 muM acetylcholine. The precise mechanism of the neutrophil-calcium interaction is presently not well understood. However, the finding that 0.5-1.0 muM A-23187 also provoked a rapid association of extracellular calcium with neutrophils suggests that calcium mobilization into the intracellular environment may account, at least in part, for this association between cells and calcium. The close temporal relationship between beta-glucuronidase secretion, cyclic GMP accumulation, and calcium mobilization during cell contact with membrane active agents such as immune reactants, acetylcholine, and ionophores suggests that these three cellular events bear a cause and effect relationship. On the basis of our findings to date, we propose that the immunologic secretion of lysosomal contents from human neutrophils is signaled by intracellular cyclic GMP and that extracellular calcium, by gaining access to the intracellular processes responsible for cyclic GMP accumulation, serves as the link to stimulus-secretion coupling.Keywords
This publication has 20 references indexed in Scilit:
- Hormonal Control of Lysosomal Enzyme Release from Human Neutrophils: Elevation of Cyclic Nucleotide Levels by Autonomic NeurohormonesProceedings of the National Academy of Sciences, 1974
- Hormonal Control of Neutrophil Lysosomal Enzyme Release: Effect of Epinephrine on Adenosine 3′,5′-MonophosphateScience, 1974
- Cyclic GMP and Cell MovementNature, 1973
- Regulation of levels of guanosine cyclic 3',5'-monophosphate in the central nervous system: effects of depolarizing agents.1973
- Inosine 3′,5′-monophosphate and adenosine 3′,5′-monophosphate-dependent protein kinase from human PMN leucocytesBiochemical and Biophysical Research Communications, 1972
- Guanosine 3′:5′-Cyclic Monophosphate: A Possible Intracellular Mediator of Mitogenic Influences in LymphocytesProceedings of the National Academy of Sciences, 1972
- THE FORMATION AND METABOLISM OF CYCLIC GMP*Annals of the New York Academy of Sciences, 1971
- Adenyl cyclase in human leukocytes: evidence for activation by separate beta adrenergic and prostaglandin receptors.1971
- The role of calcium in the release of neurotransmitter substances and hormones.1970
- The accumulation of calcium by the polymorphonuclear leucocyte treated with staphylococcal leucocidin and its significance in the extrusion of proteinBiochemical Journal, 1963