Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1985 Jul;120(1):112–120.

Activated rat neutrophils. Correlation of arachidonate products with enzyme secretion but not with O(2)- generation.

P A Ward, M C Sulavik, K J Johnson
PMCID: PMC1887955  PMID: 2990221

Abstract

Functional responses (enzyme secretion and generation of O2-) have been studied in rat neutrophils with the use of a variety of different agonists which vary in their ability to activate neutrophils. Concomitantly, the authors have analyzed the cells for production of cyclooxygenase (PGE2, PGF2 alpha, and TXB2) and lipoxygenase (monoHETEs and LTB4) products in order to determine whether there is a correlation between functional responses and arachidonate products in stimulated neutrophils. The studies indicate that enzyme secretion is closely correlated with generation of arachidonate (cyclooxygenase as well as lipoxygenase) products. These responses are dependent on the dose of agonist employed, but there does not appear to be a unique pattern of arachidonate products that can be attributed to a specific agonist. With respect to monohydroxyeicosatetraenoic acid (monoHETE) generation, we demonstrate that stimulated rat neutrophils selectively produce 5-HETE, to the virtual exclusion of 12-HETE and 15-HETE. The production of O2- from stimulated rat neutrophils is correlated neither with enzyme secretion nor with the generation of arachidonate products. These studies suggest that enzyme secretion and O2- generation are mediated by two fundamentally different intracellular pathways, even though these functional responses probably derive from common agonist-receptor interactions on the plasma membrane.

Full text

PDF
112

Selected References

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

  1. Bailey P. J., Sturm A. Immune complexes and inflammation. A study of the activity of anti-inflammatory drugs in the reverse passive arthus reaction in the rat. Biochem Pharmacol. 1983 Feb 1;32(3):475–481. doi: 10.1016/0006-2952(83)90526-9. [DOI] [PubMed] [Google Scholar]
  2. Bokoch G. M., Reed P. W. Stimulation of arachidonic acid metabolism in the polymorphonuclear leukocyte by an N-formylated peptide. Comparison with ionophore A23187. J Biol Chem. 1980 Nov 10;255(21):10223–10226. [PubMed] [Google Scholar]
  3. Borgeat P., Samuelsson B. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A. 1979 May;76(5):2148–2152. doi: 10.1073/pnas.76.5.2148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  5. Clancy R. M., Dahinden C. A., Hugli T. E. Arachidonate metabolism by human polymorphonuclear leukocytes stimulated by N-formyl-Met-Leu-Phe or complement component C5a is independent of phospholipase activation. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7200–7204. doi: 10.1073/pnas.80.23.7200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goetzl E. J., Foster D. W., Goldman D. W. Isolation and partial characterization of membrane protein constituents of human neutrophil receptors for chemotactic formylmethionyl peptides. Biochemistry. 1981 Sep 29;20(20):5717–5722. doi: 10.1021/bi00523a013. [DOI] [PubMed] [Google Scholar]
  7. Goetzl E. J., Sun F. F. Generation of unique mono-hydroxy-eicosatetraenoic acids from arachidonic acid by human neutrophils. J Exp Med. 1979 Aug 1;150(2):406–411. doi: 10.1084/jem.150.2.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ham E. A., Soderman D. D., Zanetti M. E., Dougherty H. W., McCauley E., Kuehl F. A., Jr Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4349–4353. doi: 10.1073/pnas.80.14.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Humes J. L., Burger S., Galavage M., Kuehl F. A., Jr, Wightman P. D., Dahlgren M. E., Davies P., Bonney R. J. The diminished production of arachidonic acid oxygenation products by elicited mouse peritoneal macrophages: possible mechanisms. J Immunol. 1980 May;124(5):2110–2116. [PubMed] [Google Scholar]
  10. Kajikawa N., Kaibuchi K., Matsubara T., Kikkawa U., Takai Y., Nishizuka Y., Itoh K., Tomioka C. A possible role of protein kinase C in signal-induced lysosomal enzyme release. Biochem Biophys Res Commun. 1983 Oct 31;116(2):743–750. doi: 10.1016/0006-291x(83)90587-9. [DOI] [PubMed] [Google Scholar]
  11. Kaplan H. B., Edelson H. S., Korchak H. M., Given W. P., Abramson S., Weissmann G. Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo. Biochem Pharmacol. 1984 Feb 1;33(3):371–378. doi: 10.1016/0006-2952(84)90228-4. [DOI] [PubMed] [Google Scholar]
  12. Kunkel S. L., Chensue S. W., Mouton C., Higashi G. I. Role of lipoxygenase products in murine pulmonary granuloma formation. J Clin Invest. 1984 Aug;74(2):514–524. doi: 10.1172/JCI111449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kunkel S. L., Kaercher K., Plewa M., Fantone J. C., Ward P. A. Production of cyclooxygenase products and superoxide anion by macrophages in response to chemotactic factors. Prostaglandins. 1982 Dec;24(6):789–799. doi: 10.1016/0090-6980(82)90059-4. [DOI] [PubMed] [Google Scholar]
  14. Kunkel S. L., Thrall R. S., Kunkel R. G., McCormick J. R., Ward P. A., Zurier R. B. Suppression of immune complex vasculitis in rats by prostaglandin. J Clin Invest. 1979 Nov;64(5):1525–1529. doi: 10.1172/JCI109611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lewis R. A., Austen K. F. The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. J Clin Invest. 1984 Apr;73(4):889–897. doi: 10.1172/JCI111312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lindgren J. A., Hansson G., Samuelsson B. Formation of novel hydroxylated eicosatetraenoic acids in preparations of human polymorphonuclear leukocytes. FEBS Lett. 1981 Jun 15;128(2):329–335. doi: 10.1016/0014-5793(81)80110-x. [DOI] [PubMed] [Google Scholar]
  17. Manderino G. L., Suarez A. F., Kunkel S. L., Ward P. A., Hirata A. A., Showell H. Purification of human C5a des arg by immunoadsorbent and molecular sieve chromatography. J Immunol Methods. 1982 Aug 27;53(1):41–50. doi: 10.1016/0022-1759(82)90238-1. [DOI] [PubMed] [Google Scholar]
  18. Naccache P. H., Molski T. F., Becker E. L., Borgeat P., Picard S., Vallerand P., Sha'afi R. I. Specificity of the effect of lipoxygenase metabolites of arachidonic acid on calcium homeostasis in neutrophils. Correlation with functional activity. J Biol Chem. 1982 Aug 10;257(15):8608–8611. [PubMed] [Google Scholar]
  19. Niedel J. E., Kuhn L. J., Vandenbark G. R. Phorbol diester receptor copurifies with protein kinase C. Proc Natl Acad Sci U S A. 1983 Jan;80(1):36–40. doi: 10.1073/pnas.80.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. O'Flaherty J. T., Showell H. J., Becker E. L., Ward P. A. Neutrophil aggregation and degranulation. Effect of arachidonic acid. Am J Pathol. 1979 May;95(2):433–444. [PMC free article] [PubMed] [Google Scholar]
  21. Palmer R. M., Salmon J. A. Release of leukotriene B4 from human neutrophils and its relationship to degranulation induced by N-formyl-methionyl-leucyl-phenylalanine, serum-treated zymosan and the ionophore A23187. Immunology. 1983 Sep;50(1):65–73. [PMC free article] [PubMed] [Google Scholar]
  22. Rubin R. P., Sink L. E., Schrey M. P., Day A. R., Liao C. S., Freer R. J. Secretagogues for lysosomal enzyme release as stimulants of arachidonyl phosphatidylinositol turnover in rabbit neutrophils. Biochem Biophys Res Commun. 1979 Oct 29;90(4):1364–1370. doi: 10.1016/0006-291x(79)91186-0. [DOI] [PubMed] [Google Scholar]
  23. Serhan C. N., Broekman M. J., Korchak H. M., Marcus A. J., Weissmann G. Endogenous phospholipid metabolism in stimulated neutrophils differential activation by FMLP and PMA. Biochem Biophys Res Commun. 1982 Aug;107(3):951–958. doi: 10.1016/0006-291x(82)90615-5. [DOI] [PubMed] [Google Scholar]
  24. Siegel M. I., McConnell R. T., Bonser R. W., Cuatrecasas P. The production of 5-HETE and leukotriene B in rat neutrophils from carrageenan pleural exudates. Prostaglandins. 1981 Jan;21(1):123–132. doi: 10.1016/0090-6980(81)90202-1. [DOI] [PubMed] [Google Scholar]
  25. Smith R. J., Sun F. F., Iden S. S., Bowman B. J., Sprecher H., McGuire J. C. An evaluation of the relationship between arachidonic acid lipoxygenation and human neutrophil degranulation. Clin Immunol Immunopathol. 1981 Aug;20(2):157–169. doi: 10.1016/0090-1229(81)90174-4. [DOI] [PubMed] [Google Scholar]
  26. Spagnuolo P. J., Ellner J. J., Hassid A., Dunn M. J. Thromboxane A2 mediates augmented polymorphonuclear leukocyte adhesiveness. J Clin Invest. 1980 Sep;66(3):406–414. doi: 10.1172/JCI109870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stenson W. F., Parker C. W. Metabolism of arachidonic acid in ionophore-stimulated neutrophils. Esterification of a hydroxylated metabolite into phospholipids. J Clin Invest. 1979 Nov;64(5):1457–1465. doi: 10.1172/JCI109604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Takenawa T., Homma Y., Nagai Y. Role of Ca2+ in phosphatidylinositol response and arachidonic acid release in formylated tripeptide- or Ca2+ ionophore A23187-stimulated guinea pig neutrophils. J Immunol. 1983 Jun;130(6):2849–2855. [PubMed] [Google Scholar]
  29. Verhagen J., Bruynzeel P. L., Koedam J. A., Wassink G. A., de Boer M., Terpstra G. K., Kreukniet J., Veldink G. A., Vliegenthart J. F. Specific leukotriene formation by purified human eosinophils and neutrophils. FEBS Lett. 1984 Mar 12;168(1):23–28. doi: 10.1016/0014-5793(84)80199-4. [DOI] [PubMed] [Google Scholar]
  30. Waite M., DeChatelet L. R., King L., Shirley P. S. Phagocytosis-induced release of arachidonic acid from human neutrophils. Biochem Biophys Res Commun. 1979 Oct 12;90(3):984–992. doi: 10.1016/0006-291x(79)91924-7. [DOI] [PubMed] [Google Scholar]
  31. Walsh C. E., Dechatelet L. R., Chilton F. H., Wykle R. L., Waite M. Mechanism of arachidonic acid release in human polymorphonuclear leukocytes. Biochim Biophys Acta. 1983 Jan 7;750(1):32–40. doi: 10.1016/0005-2760(83)90201-1. [DOI] [PubMed] [Google Scholar]
  32. Ward P. A., Duque R. E., Sulavik M. C., Johnson K. J. In vitro and in vivo stimulation of rat neutrophils and alveolar macrophages by immune complexes. Production of O-2 and H2O2. Am J Pathol. 1983 Mar;110(3):297–309. [PMC free article] [PubMed] [Google Scholar]
  33. Ward P. A., Sulavik M. C., Johnson K. J. Rat neutrophil activation and effects of lipoxygenase and cyclooxygenase inhibitors. Am J Pathol. 1984 Aug;116(2):223–233. [PMC free article] [PubMed] [Google Scholar]
  34. Williams L. T., Snyderman R., Pike M. C., Lefkowitz R. J. Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1204–1208. doi: 10.1073/pnas.74.3.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yano K., Hattori H., Imai A., Nozawa Y. Modification of positional distribution of fatty acids in phosphatidylinositol of rabbit neutrophils stimulated with formylmethionyl-leucyl-phenylalanine. Biochim Biophys Acta. 1983 Jun 16;752(1):137–144. doi: 10.1016/0005-2760(83)90241-2. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES