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. 1979 May;95(2):433–444.

Neutrophil aggregation and degranulation. Effect of arachidonic acid.

J T O'Flaherty, H J Showell, E L Becker, P A Ward
PMCID: PMC2042334  PMID: 453323

Abstract

In response to aggregating and degranulating stimuli, platelets metabolize endogenous arachidonic acid to bioactive derivatives. These derivatives can stimulate platelets to degranulate and aggregate and, therefore, may be mediators of the platelet response. Because exogenous arachidonic acid also stimulates platelets to degranulate, aggregate, and form these mediators, we examined the effect of adding arachidonic acid to purified human neutrophil suspensions. Micromolar concentrations of arachidonic acid stimulated neutrophils to aggregate but not to degranulate. Cytochalasin B, a potentiator of neutrophil responses to chemotactic factors, also potentiated the arachidonic-acid-induced aggregation response; 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, blocked this response. Aggregation of neutrophils, was not stimulated by several fatty acids with structural similarity to arachidonic acid. These results suggest that metabolic derivatives of arachidonic acid may be active in stimulating certain neutrophil responses. The role of these derivatives in mediating neutrophil responses to various stimuli needs to be examined.

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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. Bills T. K., Smith J. B., Silver M. J. Metabolism of [14C]arachidonic acid by human platelets. Biochim Biophys Acta. 1976 Feb 23;424(2):303–314. doi: 10.1016/0005-2760(76)90198-3. [DOI] [PubMed] [Google Scholar]
  3. Blackwell G. J., Duncombe W. G., Flower R. J., Parsons M. F., Vane J. R. The distribution and metabolism of arachidonic acid in rabbit platelets during aggregation and its modification by drugs. Br J Pharmacol. 1977 Feb;59(2):353–366. doi: 10.1111/j.1476-5381.1977.tb07500.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blackwell G. J. Phospholipase A2 and platelet aggregation. Adv Prostaglandin Thromboxane Res. 1978;3:137–142. [PubMed] [Google Scholar]
  5. Borgeat P., Hamberg M., Samuelsson B. Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases. J Biol Chem. 1976 Dec 25;251(24):7816–7820. [PubMed] [Google Scholar]
  6. Claesson H. E., Malmsten C. On the interrelationship of prostaglandin endoperoxide G2 and cyclic nucleotides in platelet function. Eur J Biochem. 1977 Jun 1;76(1):277–284. doi: 10.1111/j.1432-1033.1977.tb11593.x. [DOI] [PubMed] [Google Scholar]
  7. Craddock P. R., Hammerschmidt D., White J. G., Dalmosso A. P., Jacob H. S. Complement (C5-a)-induced granulocyte aggregation in vitro. A possible mechanism of complement-mediated leukostasis and leukopenia. J Clin Invest. 1977 Jul;60(1):260–264. doi: 10.1172/JCI108763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feinstein M. B., Becker E. L., Fraser C. Thrombin, collagen and A23187 stimulated endogenous platelet arachidonate metabolism: differential inhibition by PGE1, local anesthetics and a serine-protease inhibitor. Prostaglandins. 1977;14(6):1075–1093. doi: 10.1016/0090-6980(77)90286-6. [DOI] [PubMed] [Google Scholar]
  9. Franson R., Weiss J., Martin L., Spitznagel J. K., Elsbach P. Phospholipase A activity associated with membranes of human polymorphonuclear leucocytes. Biochem J. 1977 Dec 1;167(3):839–841. doi: 10.1042/bj1670839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fukami M. H., Holmsen H., Bauer J. Thrombin-induced oxygen consumption, malonyldialdehyde formation and serotonin secretion in human platelets. Biochim Biophys Acta. 1976 Mar 25;428(1):253–256. doi: 10.1016/0304-4165(76)90126-4. [DOI] [PubMed] [Google Scholar]
  11. Goetzl E. J., Gorman R. R. Chemotactic and chemokinetic stimulation of human eosinophil and neutrophil polymorphonuclear leukocytes by 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT). J Immunol. 1978 Feb;120(2):526–531. [PubMed] [Google Scholar]
  12. Goetzl E. J., Woods J. M., Gorman R. R. Stimulation of human eosinophil and neutrophil polymorphonuclear leukocyte chemotaxis and random migration by 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid. J Clin Invest. 1977 Jan;59(1):179–183. doi: 10.1172/JCI108617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldstein I. M., Malmsten C. L., Kindahl H., Kaplan H. B., Rådmark O., Samuelsson B., Weissmann G. Thromboxane generation by human peripheral blood polymorphonuclear leukocytes. J Exp Med. 1978 Sep 1;148(3):787–792. doi: 10.1084/jem.148.3.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldstein I. M., Malmsten C. L., Samuelsson B., Weissmann G. Prostaglandins, thromboxanes, and polymorphonuclear leukocytes: mediation and modulation of inflammation. Inflammation. 1977 Dec;2(4):309–317. doi: 10.1007/BF00921010. [DOI] [PubMed] [Google Scholar]
  15. Goldstein I., Hoffstein S., Gallin J., Weissmann G. Mechanisms of lysosomal enzyme release from human leukocytes: microtubule assembly and membrane fusion induced by a component of complement. Proc Natl Acad Sci U S A. 1973 Oct;70(10):2916–2920. doi: 10.1073/pnas.70.10.2916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Granström E., Kindahl H., Samuelsson B. A method for measuring the unstable thromboxane A2: radioimmunoassay of the derived mono-O-methyl-thromboxane B2. Prostaglandins. 1976 Dec;12(6):929–941. doi: 10.1016/0090-6980(76)90127-1. [DOI] [PubMed] [Google Scholar]
  17. Hamberg M., Samuelsson B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3400–3404. doi: 10.1073/pnas.71.9.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hamberg M., Svensson J., Samuelsson B. Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins. Proc Natl Acad Sci U S A. 1974 Oct;71(10):3824–3828. doi: 10.1073/pnas.71.10.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hamberg M., Svensson J., Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994–2998. doi: 10.1073/pnas.72.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Hammarström S., Falardeau P. Resolution of prostaglandin endoperoxide synthase and thromboxane synthase of human platelets. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3691–3695. doi: 10.1073/pnas.74.9.3691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Henson P. M. The immunologic release of constituents from neutrophil leukocytes. I. The role of antibody and complement on nonphagocytosable surfaces or phagocytosable particles. J Immunol. 1971 Dec;107(6):1535–1546. [PubMed] [Google Scholar]
  23. Higgs G. A., McCall E., Youlten L. J. A chemotactic role for prostaglandins released from polymorphonuclear leucocytes during phagocytosis. Br J Pharmacol. 1975 Apr;53(4):539–546. doi: 10.1111/j.1476-5381.1975.tb07392.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hill H. R., Estensen R. D., Quie P. G., Hogan N. A., Goldberg N. D. Modulation of human neutrophil chemotactic responses by cyclic 3',5'-guanosine monophosphate and cyclic 3',5'-adenosine monophosphate. Metabolism. 1975 Mar;24(3):447–456. doi: 10.1016/0026-0495(75)90124-9. [DOI] [PubMed] [Google Scholar]
  25. Kinlough-Rathbone R. L., Reimers H. J., Mustard J. F., Packham M. A. Sodium arachidonate can induce platelet shape change and aggregation which are independent of the release reaction. Science. 1976 Jun 4;192(4243):1011–1012. doi: 10.1126/science.1273582. [DOI] [PubMed] [Google Scholar]
  26. Kitchen E. A., Boot J. R., Dawson W. Chemotactic activity of thromboxane B2, prostaglandins and their metabolites for polymorphonuclear leucocytes. Prostaglandins. 1978 Aug;16(2):239–244. doi: 10.1016/0090-6980(78)90025-4. [DOI] [PubMed] [Google Scholar]
  27. Malmsten C., Hamberg M., Svensson J., Samuelsson B. Physiological role of an endoperoxide in human platelets: hemostatic defect due to platelet cyclo-oxygenase deficiency. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1446–1450. doi: 10.1073/pnas.72.4.1446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mason R. J., Stossel T. P., Vaughan M. Lipids of alveolar macrophages, polymorphonuclear leukocytes, and their phagocytic vesicles. J Clin Invest. 1972 Sep;51(9):2399–2407. doi: 10.1172/JCI107052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McCall E., Youlten L. J. Proceedings: Prostaglandin E1 synthesis by phagocytosing rabbit polymorphonuclear leucocytes: its inhibition by indomethacin and its role in chemotaxis. J Physiol. 1973 Oct;234(2):98P–100P. [PubMed] [Google Scholar]
  30. Minkes M., Stanford N., Chi M. M., Roth G. J., Raz A., Needleman P., Majerus P. W. Cyclic adenosine 3',5'-monophosphate inhibits the availability of arachidonate to prostaglandin synthetase in human platelet suspensions. J Clin Invest. 1977 Mar;59(3):449–454. doi: 10.1172/JCI108659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Needleman P., Minkes M., Raz A. Thromboxanes: selective biosynthesis and distinct biological properties. Science. 1976 Jul 9;193(4248):163–165. doi: 10.1126/science.945611. [DOI] [PubMed] [Google Scholar]
  32. Nugteren D. H. Arachidonate lipoxygenase in blood platelets. Biochim Biophys Acta. 1975 Feb 20;380(2):299–307. doi: 10.1016/0005-2760(75)90016-8. [DOI] [PubMed] [Google Scholar]
  33. O'Flaherty J. T., Kreutzer D. L., Showell H. J., Ward P. A. Influence of inhibitors of cellular function on chemotactic factor-induced neutrophil aggregation. J Immunol. 1977 Nov;119(5):1751–1756. [PubMed] [Google Scholar]
  34. O'Flaherty J. T., Kreutzer D. L., Ward P. A. Chemotactic factor influences on the aggregation, swelling, and foreign surface adhesiveness of human leukocytes. Am J Pathol. 1978 Mar;90(3):537–550. [PMC free article] [PubMed] [Google Scholar]
  35. O'Flaherty J. T., Kreutzer D. L., Ward P. A. Neutrophil aggregation and swelling induced by chemotactic agents. J Immunol. 1977 Jul;119(1):232–239. [PubMed] [Google Scholar]
  36. O'Flaherty J. T., Showell H. J., Becker E. L., Ward P. A. Substances which aggregate neutrophils. Mechanism of action. Am J Pathol. 1978 Jul;92(1):155–166. [PMC free article] [PubMed] [Google Scholar]
  37. O'Flaherty J. T., Showell H. J., Ward P. A. Influence of extracellular Ca2+ and Mg2+ on chemotactic factor-induced neutrophil aggregation. Inflammation. 1977 Dec;2(4):265–276. doi: 10.1007/BF00921006. [DOI] [PubMed] [Google Scholar]
  38. Oelz O., Knapp H. R., Roberts L. J., Oelz R., Sweetman B. J., Oates J. A., Reed P. W. Calcium-dependent stimulation of thromboxane and prostaglandin biosynthesis by ionophores. Adv Prostaglandin Thromboxane Res. 1978;3:147–158. [PubMed] [Google Scholar]
  39. Rivkin I., Rosenblatt J., Becker E. L. The role of cyclic AMP in the chemotactic responsiveness and spontaneous motility of rabbit peritoneal neutrophils. The inhibition of neutrophil movement and the elevation of cyclic AMP levels by catecholamines, prostaglandins, theophylline and cholera toxin. J Immunol. 1975 Oct;115(4):1126–1134. [PubMed] [Google Scholar]
  40. Sahu S., Lynn W. S. Lipid chemotaxins isolated from culture filtrates of Escherichia coli and from oxidized lipids. Inflammation. 1977 Mar;2(1):47–54. doi: 10.1007/BF00920874. [DOI] [PubMed] [Google Scholar]
  41. Salzman E. W. Prostaglandins and platelet function. Adv Prostaglandin Thromboxane Res. 1976;2:767–780. [PubMed] [Google Scholar]
  42. Samuelsson B., Folco G., Granström E., Kindahl H., Malmsten C. Prostaglandins and thromboxanes: biochemical and physiological considerations. Adv Prostaglandin Thromboxane Res. 1978;4:1–25. [PubMed] [Google Scholar]
  43. Silver M. J., Hoch W., Kocsis J. J., Ingerman C. M., Smith J. B. Arachidonic acid causes sudden death in rabbits. Science. 1974 Mar 15;183(4129):1085–1087. doi: 10.1126/science.183.4129.1085. [DOI] [PubMed] [Google Scholar]
  44. Silver M. J., Smith J. B., Ingerman C., Kocsis J. J. Arachidonic acid-induced human platelet aggregation and prostaglandin formation. Prostaglandins. 1973 Dec;4(6):863–875. doi: 10.1016/0090-6980(73)90121-4. [DOI] [PubMed] [Google Scholar]
  45. Smith J. B., Ingerman C., Kocsis J. J., Silver M. J. Formation of an intermediate in prostaglandin biosynthesis and its association with the platelet release reaction. J Clin Invest. 1974 May;53(5):1468–1472. doi: 10.1172/JCI107695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Smith J. B., Ingerman C., Silver M. J. Persistence of thromboxane A2-like material and platelet release-inducing activity in plasma. J Clin Invest. 1976 Nov;58(5):1119–1122. doi: 10.1172/JCI108564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Smolen J. E., Shohet S. B. Remodeling of granulocyte membrane fatty acids during phagocytosis. J Clin Invest. 1974 Mar;53(3):726–734. doi: 10.1172/JCI107611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Stossel T. P., Mason R. J., Smith A. L. Lipid peroxidation by human blood phagocytes. J Clin Invest. 1974 Sep;54(3):638–645. doi: 10.1172/JCI107801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Tainer J. A., Turner S. R., Lynn W. S. New aspects of chemotaxis. Specific target-cell attraction by lipid and lipoprotein fractions of Escherichia coli chemotactic factor. Am J Pathol. 1975 Nov;81(2):401–410. [PMC free article] [PubMed] [Google Scholar]
  50. Tolone G., Bonasera L., Brai M., Tolone C. Prostaglandin production by human polymorphnuclear leucocytes during phagocytosis in vitro. Experientia. 1977 Jul 15;33(7):961–962. doi: 10.1007/BF01951305. [DOI] [PubMed] [Google Scholar]
  51. Turner S. R., Campbell J. A., Lynn W. S. Polymorphonulcear leukocyte chemotaxis toward oxidized lipid components of cell membranes. J Exp Med. 1975 Jun 1;141(6):1437–1441. doi: 10.1084/jem.141.6.1437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Turner S. R., Tainer J. A., Lynn W. S. Biogenesis of chemotactic molecules by the arachidonate lipoxygenase system of platelets. Nature. 1975 Oct 23;257(5528):680–681. doi: 10.1038/257680a0. [DOI] [PubMed] [Google Scholar]
  53. Vargaftig B. B., Zirinis P. Platelet aggregation induced by arachidonic acid is accompanied by release of potential inflammatory mediators distinct from PGE2 and PGF2. Nat New Biol. 1973 Jul 25;244(134):114–116. doi: 10.1038/newbio244114a0. [DOI] [PubMed] [Google Scholar]
  54. Vincent J. E., Zijlstra F. J. Formation by phospholipase A2 of prostaglandins and endoperoxides in platelets of normal and essential fatty acid-deficient rats. Adv Prostaglandin Thromboxane Res. 1978;3:143–146. [PubMed] [Google Scholar]
  55. Willis A. L. Isolation of a chemical trigger for thrombosis. Prostaglandins. 1974 Jan 10;5(1):1–25. doi: 10.1016/s0090-6980(74)80126-7. [DOI] [PubMed] [Google Scholar]
  56. Willis A. L., Kuhn D. C., Weiss H. J. Acetylenic analog of arachidonate that acts like aspirin on platelets. Science. 1974 Jan 25;183(4122):327–330. doi: 10.1126/science.183.4122.327. [DOI] [PubMed] [Google Scholar]
  57. Willis A. L., Vane F. M., Kuhn D. C., Scott C. G., Petrin M. An endoperoxide aggregator (Lass), formed in platelets in response to thrombotic stimuli: purification, identification and unique biological significance. Prostaglandins. 1974 Dec 25;8(6):453–507. doi: 10.1016/0090-6980(74)90062-8. [DOI] [PubMed] [Google Scholar]
  58. Zurier R. B. Prostaglandin release from human polymorphonuclear leukocytes. Adv Prostaglandin Thromboxane Res. 1976;2:815–818. [PubMed] [Google Scholar]

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