Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1977 Feb;59(2):253–259. doi: 10.1111/j.1476-5381.1977.tb07487.x

Effect of indomethacin and related drugs on the calcium ion-dependent secretion of lysosomal and other enzymes by neutrophil polymorphonuclear leucocytes in vitro.

B J Northover
PMCID: PMC1667735  PMID: 402167

Abstract

1 Rabbit isolated peritoneal neutrophil polymorphonuclear leucocytes were depleted of calcium by exposure for 1 h to calcium-free bathing fluid at 4 degrees C. 2 Addition of calcium ions to the previously calcium-depleted calls during incubation at 37 degrees C stimulated the release of beta-glucuronidase and of lysozyme but not of lactate dehydrogenase. 3 Low concentrations of indomethacin, flufenamate or salicylate, such as those which occur in the blood plasma after therapeutic doses of these drugs, selectively inhibited the calcium-induced release of beta-glucuronidase. The slight release of this enzyme which occurred in the absence of added calcium ions was not altered by these drugs, neither was the release of lactate dehydrogenase. 4 Release of lysozyme was inhibited by low concentrations of salicylate, amidopyrine or oxyphenbutazone, independent of the presence or absence of calcium ions. 5 Chloroquine, hydrocortisone or colchicine did not alter the release of leucocyte enzymes.

Full text

PDF
253

Selected References

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

  1. Ackerman N. R., Beebe J. R. Effects of pharmacologic agents on release of lysosomal enzymes from alveolar mononuclear cells. J Pharmacol Exp Ther. 1975 May;193(2):603–613. [PubMed] [Google Scholar]
  2. Anderson A. J. Lysosomal enzyme activity in rats with adjuvant-induced arthritis. Ann Rheum Dis. 1970 May;29(3):307–313. doi: 10.1136/ard.29.3.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson A. J. The effect of anti-inflammatory drugs on the enzymic activity of a rat liver granular fraction which increases vascular permeability. Biochem Pharmacol. 1968 Nov;17(11):2253–2264. doi: 10.1016/0006-2952(68)90032-4. [DOI] [PubMed] [Google Scholar]
  4. Baggiolini M., Hirsch J. G., De Duve C. Further biochemical and morphological studies of granule fractions from rabbit heterophil leukocytes. J Cell Biol. 1970 Jun;45(3):586–597. doi: 10.1083/jcb.45.3.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baggiolini M., Hirsch J. G., De Duve C. Resolution of granules from rabbit heterophil leukocytes into distinct populations by zonal sedimentation. J Cell Biol. 1969 Feb;40(2):529–541. doi: 10.1083/jcb.40.2.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bainton D. F., Farquhar M. G. Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. I. Histochemical staining of bone marrow smears. J Cell Biol. 1968 Nov;39(2):286–298. doi: 10.1083/jcb.39.2.286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bainton D. F., Farquhar M. G. Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes. II. Cytochemistry and electron microscopy of bone marrow cells. J Cell Biol. 1968 Nov;39(2):299–317. doi: 10.1083/jcb.39.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bainton D. F., Farquhar M. G. Origin of granules in polymorphonuclear leukocytes. Two types derived from opposite faces of the Golgi complex in developing granulocytes. J Cell Biol. 1966 Feb;28(2):277–301. doi: 10.1083/jcb.28.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Dewald B., Rindler-Ludwig R., Bretz U., Baggiolini M. Subcellular localization and heterogeneity of neutral proteases in neutrophilic polymorphonuclear leukocytes. J Exp Med. 1975 Apr 1;141(4):709–723. doi: 10.1084/jem.141.4.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FISHMAN W. H. Beta-glucuronidase. Adv Enzymol Relat Subj Biochem. 1955;16:361–409. doi: 10.1002/9780470122617.ch7. [DOI] [PubMed] [Google Scholar]
  12. Goldstein I. M. Effect of steroids on lysosomes. Transplant Proc. 1975 Mar;7(1):21–24. [PubMed] [Google Scholar]
  13. Goldstein I. M., Hoffstein S. T., Weissmann G. Influence of divalent cations upon complement-mediated enzyme release from human polymorphonuclear leukocytes. J Immunol. 1975 Sep;115(3):665–670. [PubMed] [Google Scholar]
  14. Goldstein I. M., Horn J. K., Kaplan H. B., Weissmann G. Calcium-induced lysozyme secretion from human polymorphonuclear leukocytes. Biochem Biophys Res Commun. 1974 Sep 23;60(2):807–812. doi: 10.1016/0006-291x(74)90312-x. [DOI] [PubMed] [Google Scholar]
  15. Hawkins D. Neutrophilic leukocytes in immunologic reactions in vitro. 3. Pharmacologic modulation of lysosomal constituent release. Clin Immunol Immunopathol. 1974 Jan;2(2):141–152. doi: 10.1016/0090-1229(74)90034-8. [DOI] [PubMed] [Google Scholar]
  16. Henson P. M. Pathologic mechanisms in neutrophil-mediated injury. Am J Pathol. 1972 Sep;68(3):593–612. [PMC free article] [PubMed] [Google Scholar]
  17. Hvidberg E., Lausen H. H., Jansen J. A. Indomethacin: plasma concentrations and protein binding in man. Eur J Clin Pharmacol. 1972 Mar;4(2):119–124. doi: 10.1007/BF00562508. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Ignarro L. J. Nonphagocytic release of neutral protease and beta-glucuronidase from human neutrophils. Regulation by autonomic neurohormones and cyclic nucleotides. Arthritis Rheum. 1974 Jan-Feb;17(1):25–36. doi: 10.1002/art.1780170106. [DOI] [PubMed] [Google Scholar]
  20. Ignarro L. J. Release of neutral protease and beta-glucuronidase from human neutrophils in the presence of cartilage treated with various immunologic reactants. J Immunol. 1974 Jul;113(1):298–308. [PubMed] [Google Scholar]
  21. Malawista S. E. Microtubules and the mobilization of lysosomes in phagocytizing human leukocytes. Ann N Y Acad Sci. 1975 Jun 30;253:738–749. doi: 10.1111/j.1749-6632.1975.tb19242.x. [DOI] [PubMed] [Google Scholar]
  22. NORTHOVER B. J. THE ACTION OF ANTI-INFLAMMATORY COMPOUNDS IN MICE WITH PERITONITIS. J Pathol Bacteriol. 1964 Apr;87:395–404. doi: 10.1002/path.1700870219. [DOI] [PubMed] [Google Scholar]
  23. NORTHOVER B. J. The permeability to plasma proteins of the peritoneal blood vessels of the mouse, and the effect of substances that alter permeability. J Pathol Bacteriol. 1963 Apr;85:361–370. doi: 10.1002/path.1700850214. [DOI] [PubMed] [Google Scholar]
  24. Northover A. M. Action of histamine on endothelial cells of guinea-pig isolated hepatic portal vein and its modification by indomethacin or removal of calcium. Br J Exp Pathol. 1975 Feb;56(1):52–61. [PMC free article] [PubMed] [Google Scholar]
  25. Northover B. J. Effect of anti-inflammatory drugs on the binding of calcium to cellular membranes in various human and guinea-pig tissues. Br J Pharmacol. 1973 Jul;48(3):496–504. doi: 10.1111/j.1476-5381.1973.tb08356.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Northover B. J. Effect of anti-inflammatory drugs on the membrane potential of vascular endothelial cells in vitro. Br J Pharmacol. 1975 Jan;53(1):113–120. doi: 10.1111/j.1476-5381.1975.tb07337.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Northover B. J. Interaction of mono- and divalent metallic cations and of indomethacin on the membrane potential of vascular endothelial cells in vitro. Br J Pharmacol. 1975 Sep;55(1):105–110. doi: 10.1111/j.1476-5381.1975.tb07617.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Northover B. J. Mechanism of the inhibitory action of indomethacin on smooth muscle. Br J Pharmacol. 1971 Mar;41(3):540–551. doi: 10.1111/j.1476-5381.1971.tb08052.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Northover B. J. The effects of indomethacin on calcium, sodium, potassium and magnesium fluxes in various tissues of the guinea-pig. Br J Pharmacol. 1972 Aug;45(4):651–659. doi: 10.1111/j.1476-5381.1972.tb08124.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Oronsky A. L., Perper R. J. Connective tissue-degrading enzymes of human leukocytes. Ann N Y Acad Sci. 1975 Jun 13;256:233–253. doi: 10.1111/j.1749-6632.1975.tb36050.x. [DOI] [PubMed] [Google Scholar]
  31. Oronsky A., Ignarro L., Perper R. Release of cartilage mucopolysaccharide-degrading neutral protease from human leukocytes. J Exp Med. 1973 Aug 1;138(2):461–472. doi: 10.1084/jem.138.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Paulus H. E., Siegel M., Mongan E., Okun R., Calabro J. J. Variations of serum concentrations and half-life of salicylate in patients with rheumatoid arthritis. Arthritis Rheum. 1971 Jul-Aug;14(4):527–532. doi: 10.1002/art.1780140412. [DOI] [PubMed] [Google Scholar]
  33. Perper R. J., Oronsky A. L. Enzyme release from human leukocytes and degradation of cartilage matrix. Effects of antirheumatic drugs. Arthritis Rheum. 1974 Jan-Feb;17(1):47–55. doi: 10.1002/art.1780170108. [DOI] [PubMed] [Google Scholar]
  34. Rajan K. T. Lysosomes and gout. Nature. 1966 May 28;210(5039):959–960. doi: 10.1038/210959a0. [DOI] [PubMed] [Google Scholar]
  35. Rothermich N. O. An extended study of indomethacin. I. Clinical pharmacology. JAMA. 1966 Feb 14;195(7):531–536. [PubMed] [Google Scholar]
  36. SMOLELIS A. N., HARTSELL S. E. The determination of lysozyme. J Bacteriol. 1949 Dec;58(6):731–736. doi: 10.1128/jb.58.6.731-736.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. WOODIN A. M., WIENEKE A. A. The accumulation of calcium by the polymorphonuclear leucocyte treated with staphylococcal leucocidin and its significance in the extrusion of protein. Biochem J. 1963 Jun;87:487–495. doi: 10.1042/bj0870487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wright D. G., Malawista S. E. Mobilization and extracellular release of granular enzymes from human leukocytes during phagocytosis: inhibition by colchicine and cortisol but not by salicylate. Arthritis Rheum. 1973 Nov-Dec;16(6):749–758. doi: 10.1002/art.1780160608. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES