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. 1980 May;65(5):1077–1085. doi: 10.1172/JCI109760

Increased levels of cyclic adenosine-3',5'-monophosphate in human polymorphonuclear leukocytes after surface stimulation.

J E Smolen, H M Korchak, G Weissmann
PMCID: PMC371438  PMID: 6245105

Abstract

Levels of cyclic AMP (cAMP) (but not cyclic GMP) in suspensions of human polymorphonuclear leukocytes (PMN) increased promptly after exposure of the cells to stimuli such as the chemotactic peptide N-formyl methionyl leucyl phenylalanine, the immune complex bovine serum albumin/anti-bovine serum albumin and calcium ionophore A23187. cAMP increased rapidly, reaching a maximum of twice the basal level 10--45 s after stimulation; after 2--5 min the amount of cAMP had subsided to basal levels. Elevations in cAMP levels were concurrent with, or followed, membrane hyperpolarization (measured by uptake of the lipophilic cation triphenylmethyl phosphonium) and always preceded lysosomal enzyme release and superoxide anion (O2) production. Elevated cAMP levels could be uncoupled from these later events by removal of extracellular divalent cations, replacement of extracellular Na+ with K+ or choline+, and by use of low concentrations of stimulus; each of these conditions virtually abolished lysosomal enzyme release and O2 generation, while leaving the stimulated elevation of cAMP levels unimpaired. Calcium ionophore A23187 did not provoke membrane hyperpolarization, thus uncoupling changes in membrane potential from changes in cAMP levels. These data suggested that cAMP is not a critical component in the earliest steps of stimulus-secretion coupling. Surface stimulation of cells pretreated with prostaglandins E1 or I2 yielded very high levels of cAMP; these high levels may be an important part of the mechanism by which stable prostaglandins inhibit lysosomal enzyme release and O2 generation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Becker E. L., Showell H. J. The ability of chemotactic factors to induce lysosomal enzyme release. II. The mechanism of release. J Immunol. 1974 Jun;112(6):2055–2062. [PubMed] [Google Scholar]
  2. Berlin R. D., Fera J. P. Changes in membrane microviscosity associated with phagocytosis: effects of colchicine. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1072–1076. doi: 10.1073/pnas.74.3.1072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  4. Cohen H. J., Chovaniec M. E. Superoxide generation by digitonin-stimulated guinea pig granulocytes. A basis for a continuous assay for monitoring superoxide production and for the study of the activation of the generating system. J Clin Invest. 1978 Apr;61(4):1081–1087. doi: 10.1172/JCI109007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldstein I. M., Lind S., Hoffstein S., Weissmann G. Influence of local anesthetics upon human polymorphonuclear leukocyte function in vitro. Reduction of lysosomal enzyme release and superoxide anion production. J Exp Med. 1977 Aug 1;146(2):483–494. doi: 10.1084/jem.146.2.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hamberg M., Svensson J., Wakabayashi T., Samuelsson B. Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proc Natl Acad Sci U S A. 1974 Feb;71(2):345–349. doi: 10.1073/pnas.71.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Herlin T., Petersen C. S., Esmann V. The role of calcium and cyclic adenosine 3',5'-monophosphate in the regulation of glycogen metabolism in phagocytozing human polymorphonuclear leukocytes. Biochim Biophys Acta. 1978 Aug 3;542(1):63–76. doi: 10.1016/0304-4165(78)90233-7. [DOI] [PubMed] [Google Scholar]
  8. Hirata F., Strittmatter W. J., Axelrod J. beta-Adrenergic receptor agonists increase phospholipid methylation, membrane fluidity, and beta-adrenergic receptor-adenylate cyclase coupling. Proc Natl Acad Sci U S A. 1979 Jan;76(1):368–372. doi: 10.1073/pnas.76.1.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ignarro L. J., George W. J. Hormonal control of lysosomal enzyme release from human neutrophils: elevation of cyclic nucleotide levels by autonomic neurohormones. Proc Natl Acad Sci U S A. 1974 May;71(5):2027–2031. doi: 10.1073/pnas.71.5.2027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ignarro L. J., George W. J. Mediation of immunologic discharge of lysosomal enzymes from human neutrophils by guanosine 3',5'-monophosphate. Requirement of calcium, and inhibition by adenosine 3',5'-monophosphate. J Exp Med. 1974 Jul 1;140(1):225–238. doi: 10.1084/jem.140.1.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ignarro L. J., Lint T. F., George W. J. Hormonal control of lysosomal enzyme release from human neutrophils. Effects of autonomic agents on enzyme release, phagocytosis, and cylic nucleotide levels. J Exp Med. 1974 Jun 1;139(6):1395–1414. doi: 10.1084/jem.139.6.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ignarro L. J., Paddock R. J., George W. J. Hormonal control of neutrophil lysosomal enzyme release: effect of epinephrine on adenosine 3',5'-monophosphate. Science. 1974 Mar 1;183(4127):855–857. doi: 10.1126/science.183.4127.855. [DOI] [PubMed] [Google Scholar]
  13. Korchak H. M., Weissmann G. Changes in membrane potential of human granulocytes antecede the metabolic responses to surface stimulation. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3818–3822. doi: 10.1073/pnas.75.8.3818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Larner E. H., Rutherford C. An artifact produced by boiling adenyl cyclase reaction mixtures prior to the cyclic AMP-radioimmunoassay. Anal Biochem. 1978 Dec;91(2):684–690. doi: 10.1016/0003-2697(78)90555-9. [DOI] [PubMed] [Google Scholar]
  15. Malawista S. E., Oliver J. M., Rudolph S. A. Microtubules and cyclic AMP in human leukocytes: on the order of things. J Cell Biol. 1978 Jun;77(3):881–886. doi: 10.1083/jcb.77.3.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Manganiello V., Evans W. H., Stossel T. P., Mason R. J., Vaughan M. The effect of polystyrene beads on cyclic 3',5'-adenosine monophosphate concentration in leukocytes. J Clin Invest. 1971 Dec;50(12):2741–2744. doi: 10.1172/JCI106775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Naccache P. H., Showell H. J., Becker E. L., Sha'afi R. I. Changes in ionic movements across rabbit polymorphonuclear leukocyte membranes during lysosomal enzyme release. Possible ionic basis for lysosomal enzyme release. J Cell Biol. 1977 Dec;75(3):635–649. doi: 10.1083/jcb.75.3.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Petersen C. S., Herlin T., Esmann V. Effects of catecholamines and glucagon on glycogen metabolism in human polymorphonuclear leukocytes. Biochim Biophys Acta. 1978 Aug 3;542(1):77–87. doi: 10.1016/0304-4165(78)90234-9. [DOI] [PubMed] [Google Scholar]
  19. Schell-Frederick E., Van Sande J. Evidence that cyclic AMP is not the chemical mediator of the metabolic changes accompanying phagocytosis. J Reticuloendothel Soc. 1974 Feb;15(2):139–148. [PubMed] [Google Scholar]
  20. Showell H. J., Naccache P. H., Sha'afi R. I., Becker E. L. The effects of extracellular K+, Na+ and Ca++ on lysosomal enzyme secretion from polymorphonuclear leukocytes. J Immunol. 1977 Sep;119(3):804–811. [PubMed] [Google Scholar]
  21. Smith R. J., Ignarro L. J. Bioregulation of lysosomal enzyme secretion from human neutrophils: roles of guanosine 3':5'-monophosphate and calcium in stimulus-secretion coupling. Proc Natl Acad Sci U S A. 1975 Jan;72(1):108–112. doi: 10.1073/pnas.72.1.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Stolc V. Regulation of iodine metabolism in human leukocytes by adenosine 3',5' -monophosphate. Biochim Biophys Acta. 1972 Apr 21;264(2):285–288. doi: 10.1016/0304-4165(72)90292-9. [DOI] [PubMed] [Google Scholar]
  23. Stolc V. Restrained adenyl cyclase in human neutrophils: stimulation of cyclic adenosine 3':5'-monophosphate formation and adenyl cyclase activity by phagocytosis and prostaglandins. Blood. 1974 May;43(5):743–748. [PubMed] [Google Scholar]
  24. Ward P. A., Zvaifler N. J. Quantitative phagocytosis by neutrophils. I. A new method with immune complexes. J Immunol. 1973 Dec;111(6):1771–1776. [PubMed] [Google Scholar]
  25. Zurier R. B., Hoffstein S., Weissmann G. Mechanisms of lysosomal enzyme release from human leukocytes. I. Effect of cyclic nucleotides and colchicine. J Cell Biol. 1973 Jul;58(1):27–41. doi: 10.1083/jcb.58.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zurier R. B., Weissmann G., Hoffstein S., Kammerman S., Tai H. H. Mechanisms of lysosomal enzyme release from human leukocytes. II. Effects of cAMP and cGMP, autonomic agonists, and agents which affect microtubule function. J Clin Invest. 1974 Jan;53(1):297–309. doi: 10.1172/JCI107550. [DOI] [PMC free article] [PubMed] [Google Scholar]

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