Skip to main content
SpringerLink
Log in

Involvement of bivalent cations and arachidonic acid in neutrophil aggregation

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Chemotactic factors and arachidonic acid aggregate neutrophils; indomethacin and 5,8,11,14-eicosatetraynoic acid, two blockers of cellular arachidonate metabolism, inhibit these responses. Additionally, A23187, an ionophore which specifically transports bivalent cations into cells, also aggregates the neutrophils, and this response, as well as the response to chemotactic factors, requires the presence of extracellular calcium and magnesium. In this report these relationships were further studied. It was found that human neutrophil aggregation stimulated by arachidonic acid also required calcium and magnesium. Furthermore, cells preincubated with arachidonate for 4 min before exposure to the bivalent cations did not aggregate before or after this exposure and, following this exposure, were refractory to subsequent stimulation by more arachidonate, a chemotactic tripeptide (formylmethionylleucylphenylalanine), or A23187, i.e., these cells had become nonselectively desensitized to the aggregating agents. Finally, indomethacin and 5,8,11,14-eicoasatetraynoic acid inhibited the aggregation response stimulated by A23187 and their potency in doing so paralleled their potency in inhibiting the responses induced by arachidonate or the chemotactic tripeptide. Thus, the neutrophil aggregation responses induced by arachidonate, chemotactic factor, and A23187 were similarly influenced by preincubating the cells with arachidonate, had similar requirements for calcium and magnesium, and were similarly inhibited by blockers of arachidonate metabolism. It appears that bivalent cations and arachidonic acid play essential and, perhaps, interacting roles in the aggregation response to diverse stimuli.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mason, R. J., T. P. Stossel, andM. Vaughan. 1972. Lipids of alveolar macrophages, polymorphonuclear leukocytes, and their phagocytic vesicles.J. Clin. Invest. 51:2399–2407.

    Google Scholar 

  2. Smolen, J. E., andS. B. Shohet. 1974. Remodeling of granulocyte membrane fatty acids during phagocytosis.J. Clin. Invest. 53:726–734.

    Google Scholar 

  3. Hirata, F., B. A. Corcoran, K. Venkatasubramanian, E. Schiffmann, andJ. Axelrod. 1979. Chemoattractants stimulate degradation of methylated phospholipids and release of arachidonic acid in rabbit leukocytes.Proc. Natl. Acad. Sci. USA76:2640–2643.

    Google Scholar 

  4. Zurier, R. B., andD. M. Sayadoff. 1975. Release of prostaglandins from human polymorphonuclear leukocytes.Inflammation 1:93–101.

    Google Scholar 

  5. Higgs, G. A., S. Bunting, S. Moncada, andJ. R. Vane. 1976. Polymorphonuclear leukocytes produce thromboxane A2 like activity during phagocytosis.Prostaglandins 12:749–757.

    Google Scholar 

  6. Goldstein, I. M., C. L. Malmsten, H. Kindahl, H. B. Kaplan, O. Radmark, B. Samuelsson, andG. Weissmann. 1978. Thromboxane generation by human peripheral blood polymorphonuclear leukocytes.J. Exp. Med. 148:787–792.

    Google Scholar 

  7. Kaley, G., andR. Weiner. 1971. Effect of prostaglandin E1 on leukocyte migration.Nature New Biol. 234:114–115.

    Google Scholar 

  8. Higgs, G. A., E. McCall, andL. J. F. Youlten. 1975. A chemotactic role for prostaglandins released from polymorphonuclear leukocytes during phagocytosis.Br. J. Pharmacol. 53:539–546.

    Google Scholar 

  9. Borgeat, P., M. Hamberg, andB. Samuelsson. 1976. Transformation of arachidonic acid and homo-γ-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases.J. Biol. Chem. 24:7816–7820.

    Google Scholar 

  10. Borgeat, P., andB. Samuelsson. 1979. Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. Formation of a novel dihydroxyeicosatetraenoic acid.J. Biol. Chem. 254:2643–2646.

    Google Scholar 

  11. Kitchen, E. A., J. R. Boot, andW. Dawson. 1978. Chemotactic activity of thromboxane B2, prostaglandins and their metabolites for polymorphonuclear leukocytes,Prostaglandins 16:239–244.

    Google Scholar 

  12. Goetzl, E. J., F. H. Valone, V. N. Reinhold, andR. R. Gorman. 1979. Specific inhibition of the polymorphonuclear leukocyte chemotactic response to hydroxy-fatty acid metabolites of arachidonic acid by methyl ester derivatives.J. Clin. Invest. 63:1181–1186.

    Google Scholar 

  13. Lynn, W. S., andC. Mukherjee. 1978. Motility of human polymorphonuclear leukocytes. Roles of hydroxy fatty acids, other lipids, and cations.Am. J. Pathol. 91:581–593.

    Google Scholar 

  14. Nacache, P. H., J. H. Showell, E. L. Becker, andR. I. Sha'afi. 1979. Arachidonic acid induced degranulation of rabbit peritoneal neutrophils.Biochem. Biophys. Res. Commun. 87:292–299.

    Google Scholar 

  15. O'Flaherty, J. T., H. T. Showell, E. L. Becker, andP. A. Ward. 1979. Arachidonic acid aggregates neutrophils.Inflammation 3:431–436.

    Google Scholar 

  16. O'Flaherty, J. T., H. T. Showell, E. L. Becker, andP. A. Ward. 1979. Neutrophil aggregation and degranulation. Effect of arachidonic acid.Am. J. Pathol. 95:435–444.

    Google Scholar 

  17. O'Flaherty, J. T., H. T.Showell, E. L.Becker, and P. A.Ward. (1979). Role of arachidonic acid derivatives in neutrophil aggregation: A hypothesis.Prostaglandins (in press).

  18. O'flaherty, J. T., H. T. Showell, P. A. Ward, andE. L. Becker. 1979. Possible role of arachidonic acid in human neutrophil aggregation and degranulation.Am. J. Pathol. 96:799–809.

    Google Scholar 

  19. Wentzell, B., andR. M. Epand. 1978. Stimulation of the release of prostaglandins from polymorphonuclear leukocytes by the calcium ionophore A23187FEBS Lett. 86:255–258.

    Google Scholar 

  20. Borgeat, P., andB. Samuelsson. 1979. Arachidonic acid metabolism in polymorphonuclear leukocytes: Effects of ionophore A23187.Proc. Natl. Acad. Sci. USA76:2148–2152.

    Google Scholar 

  21. Smith, R. J., andL. J. Ignarro. 1975. Bioregulation of lysosomal enzyme secretion from human neutrophils: Roles of guanosine 3':5'-monophosphate and calcium in stimulussecretion coupling.Proc. Natl. Acad. Sci. USA72:108–112.

    Google Scholar 

  22. Naccache, P. H., H. T. Showell, E. L. Becker, andR. I. Sha'afi. 1977. Changes in ionic movements across rabbit polymorphonuclear leukocyte membranes during lysosomal enzyme release. Possible ionic basis for lysosomal enzyme release.J. Cell. Biol 75: 635–649.

    Google Scholar 

  23. Zabucchi, G., M. R. Soranzo, F. Rossi, andD. Romeo. 1975. Exocytosis in human polymorphonuclear leukocytes induced by A23187 and calcium.FEBS Lett. 54:44–48.

    Google Scholar 

  24. O'Flaherty, J. T., H. T. Showell, E. L. Becker, andP. A. Ward. 1978. Substances which aggregate neutrophils: Mechanism of action.Am. J. Pathol. 92:155–166.

    Google Scholar 

  25. O'Flaherty, J. T., D. L. Kreutzer, andP. A. Ward. 1979. Effect of cytochalasin B on human neutrophil aggregation.Exp. Cell. Res. 120:31–37.

    Google Scholar 

  26. O'Flaherty, J. T., D. L. Kreutzer, H. T. Showell, E. L. Becker, andP. A. Ward. 1978. Desensitization of the neutrophil aggregation response to chemotactic factors.Am. J. Pathol. 93:693–705.

    Google Scholar 

  27. O'Flaherty, J. T., P. L. Kreutzer, H. T. Showell, G. Vitbauskas, E. L. Becker, andP. A. Ward. 1979. Selective neutrophil desensitization to chemotactic factors.J. Cell. Biol. 80:564–572.

    Google Scholar 

  28. Willis, A. L., D. C. Kuhn, andH. J. Weiss. 1974. Acetylenic analog of arachidonate that acts like aspirin on platelets.Science 183:127–129.

    Google Scholar 

  29. Willis, A. L. 1974. An enzymatic mechanism for the antithrombotic and antihemostatic actions of aspirin.Science 183:325–327.

    Google Scholar 

  30. Flowers, R. J. 1974. Drugs which inhibit prostaglandin biosynthesis.Pharmacol. Rev. 26:33–67.

    Google Scholar 

  31. Egan, R. W., J. Paxton, andF. A. Keuhl. 1976. Mechanism of irreversible self-deactivation of prostaglandin synthetase.J. Biol. Chem. 23:7329–7335.

    Google Scholar 

  32. Needleman, P., M. Monkes, andA. Raz. 1976. Thromboxanes: Selective biosynthesis and distinct properties.Science 193:163–165.

    Google Scholar 

  33. O'Flaherty, J. T., D. L. Kreutzer, andP. A. Ward. 1979. Effect of prostaglandins E1, E2 and F2a on neutrophil aggregation.Prostaglandins 17:201–210.

    Google Scholar 

  34. Samuelsson, B., G. Folco, E. Granstrom, H. Kundahl, andC. Malmsten. 1978. Prostaglandins and thromboxanes: Biochemical and physiologycal considerations.Adv. Prostaglandin Thromboxane Res. 4:1–25.

    Google Scholar 

  35. Oelz, O., H. R. Knapp, L. J. Roberts, R. Oelz, B. J. Sweetman, J. A. Oates, andP. W. Reed. 1978. Calcium-dependent stimulation of thromboxane and prostaglandin biosynthesis by ionophores.Adv. Prostaglandin Thromboxane Res. 3:147–158.

    Google Scholar 

  36. Massini, P., R. Käser-Glanzmann, andE. F. Luscher. 1978. Movement of calcum ions and their role in the activation of platelets.Thrombos. Haemostas (Stuttgart) 40:212–218.

    Google Scholar 

  37. Kantor, H. S., andH. S. Hampton. 1978. Indomethacin in submicromolar concentrations inhibits cyclic AMP-dependent protein kinase.Nature 276:841–842.

    Google Scholar 

  38. Kaplan, L., J. Weiss, andP. Elsbach. 1978. Low concentrations of indomethacin inhibit phospholipase A2 of rabbit polymorphonuclear leukocytes,proc. Natl. Acad. Sci. USA75:2955–2958.

    Google Scholar 

Download references

Author information

Author notes

  1. J. T. O'Flaherty

    Present address: Department of Medicine, Division of Infectious Diseases, Bowman Gray School of Medicine, 27103, Winston-Salem, North Carolina

Authors and Affiliations

  1. Department of Immunopathology, Scripps Clinic and Research Foundation, 92037, La Jolla, California

    J. T. O'Flaherty

Authors
  1. J. T. O'Flaherty
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Publication 1877 of the Research Institute of Scripps Clinic, La Jolla, California 92037.

Supported by research grants: A1 07007 (NIH); Office of Naval Research; Council for Tobacco Research.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O'Flaherty, J.T. Involvement of bivalent cations and arachidonic acid in neutrophil aggregation. Inflammation 4, 181–194 (1980). https://doi.org/10.1007/BF00914164

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00914164

Keywords

Search

Navigation