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. 1980 Apr;39(4):491–501.

Modulation of human neutrophil function by monohydroxy-eicosatetraenoic acids.

E J Goetzl, A R Brash, A I Tauber, J A Oates, W C Hubbard
PMCID: PMC1458022  PMID: 6247265

Abstract

The generation from arachidonic acid and purification of large quantities of a series of monohydroxy-eicosatetraenoic acids (HETEs) which differed only in the position of the hydroxyl group permitted an in vitro analysis of the relative effects of the HETEs on a variety of human neutrophil functions. All of the HETEs elicited maximal neutrophil chemotactic responses of comparable magnitude, but the chemotactic potencies exhibited a distinct rank order with 5-HETE greater than 8-HETE:9-HETE (85:15, w:w) greater than 11-HETE=12-L-HETE. Peak chemotactic responses were achieved at concentrations of 1 microgram/ml for 5-HETE, 5 microgram/ml for 8-HETE:9-HETE and 10 microgram/ml for 11-HETE and 12-L-HETE. In the absence of a concentration gradient, the HETEs were similar in potency with respect to the stimulation of neutrophil chemokinesis and the enhancement of the expression of neutrophil C3b receptors. At optimally chemotactic and chemokinetic concentrations, none of the HETEs stimulated the generation of superoxide by neutrophils, altered the expression of neutrophil IgG-Fc receptors, or evoked the release of lysosomal enzymes. Methyl esterification of 5-HETE and 12-L-HETE reduced the chemotactic activity to less than 12% of that of the parent compound. The HETE methyl esters competitively inhibited the chemotactic activity of the homologous free acids by approximately 50% at equimolar concentrations, without inhibiting the chemotactic activity of formyl-methionyl peptides or of chemotactic fragments of the fifth component of complement (C5fr). The stimulus specificity of the competitive inhibition of chemotaxis by HETE methyl esters and the functional selectivity of the HETEs as compared to the formyl-methionyl peptides and C5fr, which stimulate neutrophil oxidative metabolism and lysosomal enzyme release, suggest that HETEs activate human neutrophils by a unique mechanism.

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Selected References

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

  1. Babior B. M., Curnutte J. T., McMurrich B. J. The particulate superoxide-forming system from human neutrophils. Properties of the system and further evidence supporting its participation in the respiratory burst. J Clin Invest. 1976 Oct;58(4):989–996. doi: 10.1172/JCI108553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Bass D. A., Dechatelet L. R., McCall C. E. Independent stimulation of motility and the oxidative metabolic burst of human polymorphonuclear leukocytes. J Immunol. 1978 Jul;121(1):172–178. [PubMed] [Google Scholar]
  4. Becker E. L., Showell H. J., Henson P. M., Hsu L. S. The ability of chemotactic factors to induce lysosomal enzyme release. I. The characteristics of the release, the importance of surfaces and the relation of enzyme release to chemotactic responsiveness. J Immunol. 1974 Jun;112(6):2047–2054. [PubMed] [Google Scholar]
  5. Becker E. L. Some interrelations of neutrophil chemotaxis, lysosomal enzyme secretion, and phagocytosis as revealed by synthetic peptides. Am J Pathol. 1976 Nov;85(2):385–394. [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Böyum A. Isolation of leucocytes from human blood. Further observations. Methylcellulose, dextran, and ficoll as erythrocyteaggregating agents. Scand J Clin Lab Invest Suppl. 1968;97:31–50. [PubMed] [Google Scholar]
  8. Curnutte J. T., Whitten D. M., Babior B. M. Defective superoxide production by granulocytes from patients with chronic granulomatous disease. N Engl J Med. 1974 Mar 14;290(11):593–597. doi: 10.1056/NEJM197403142901104. [DOI] [PubMed] [Google Scholar]
  9. Fearon D. T., Austen K. F., Ruddy S. Formation of a hemolytically active cellular intermediate by the interaction between properdin factors B and D and the activated third component of complement. J Exp Med. 1973 Dec 1;138(6):1305–1313. doi: 10.1084/jem.138.6.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fernandez H. N., Henson P. M., Otani A., Hugli T. E. Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions. J Immunol. 1978 Jan;120(1):109–115. [PubMed] [Google Scholar]
  11. Galliard T., Phillips D. R. Lipoxygenase from potato tubers. Partial purification and properties of an enzyme that specifically oxygenates the 9-position of linoleic acid. Biochem J. 1971 Sep;124(2):431–438. doi: 10.1042/bj1240431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gallin J. I., Wright D. G., Schiffmann E. Role of secretory events in modulating human neutrophil chemotaxis. J Clin Invest. 1978 Dec;62(6):1364–1374. doi: 10.1172/JCI109257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goetzl E. J., Austen K. F. A neutrophil-immobilizing factor derived from human leukocytes. I. Generation and partial characterization. J Exp Med. 1972 Dec 1;136(6):1564–1580. doi: 10.1084/jem.136.6.1564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goetzl E. J., Austen K. F. Stimulation of human neutrophil leukocyte aerobic glucose metabolism by purified chemotactic factors. J Clin Invest. 1974 Feb;53(2):591–599. doi: 10.1172/JCI107594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Goetzl E. J., Hoe K. Y. Chemotactic factor receptors of human PMN leucocytes. I. Effects on migration of labelling plasma membrane determinants with impermeant covalent reagents and inhibition of labelling by chemotactic factors. Immunology. 1979 Jun;37(2):407–418. [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Goetzl E. J., Valone F. H., Reinhold V. N., Gorman R. R. Specific inhibition of the polymorphonuclear leukocyte chemotactic response to hydroxy-fatty acid metabolites of arachidonic acid by methyl ester derivatives. J Clin Invest. 1979 Jun;63(6):1181–1186. doi: 10.1172/JCI109412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Goldstein I. M., Roos D., Kaplan H. B., Weissmann G. Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis. J Clin Invest. 1975 Nov;56(5):1155–1163. doi: 10.1172/JCI108191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hamberg M., Samuelsson B. On the specificity of the oxygenation of unsaturated fatty acids catalyzed by soybean lipoxidase. J Biol Chem. 1967 Nov 25;242(22):5329–5335. [PubMed] [Google Scholar]
  22. 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]
  23. Hamberg M., Samuelsson B. Prostaglandin endoperoxides. VII. Novel transformations of arachidonic acid in guinea pig lung. Biochem Biophys Res Commun. 1974 Dec 11;61(3):942–949. doi: 10.1016/0006-291x(74)90246-0. [DOI] [PubMed] [Google Scholar]
  24. Hamberg M. Steric analysis of hydroperoxides formed by lipoxygenase oxygenation of linoleic acid. Anal Biochem. 1971 Oct;43(2):515–526. doi: 10.1016/0003-2697(71)90282-x. [DOI] [PubMed] [Google Scholar]
  25. Hatch G. E., Gardner D. E., Menzel D. B. Chemiluminescence of phagocytic cells caused by N-formylmethionyl peptides. J Exp Med. 1978 Jan 1;147(1):182–195. doi: 10.1084/jem.147.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hemler M. E., Crawford C. G., Lands W. E. Lipoxygenation activity of purified prostaglandin-forming cyclooxygenase. Biochemistry. 1978 May 2;17(9):1772–1779. doi: 10.1021/bi00602a031. [DOI] [PubMed] [Google Scholar]
  27. Matthew J. A., Chan H. W., Galliard T. A simple method for the preparation of pure 9-D-hydroperoxide of linoleic acid and methyl linoleate based on the positional specificity of lipoxygenase in tomato fruit. Lipids. 1977 Mar;12(3):324–326. doi: 10.1007/BF02533358. [DOI] [PubMed] [Google Scholar]
  28. McGuire J. C., Kelly R. C., Gorman R. R., Sun F. F. Preparation and spectral properties of 12-hydroxyl eicosatetraenoic acid (HETE). Prep Biochem. 1978;8(2-3):147–153. doi: 10.1080/00327487808069056. [DOI] [PubMed] [Google Scholar]
  29. Nelson R. A., Jr, Jensen J., Gigli I., Tamura N. Methods for the separation, purification and measurement of nine components of hemolytic complement in guinea-pig serum. Immunochemistry. 1966 Mar;3(2):111–135. doi: 10.1016/0019-2791(66)90292-8. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. O'Flaherty J. T., Showell H. J., Kreutzer D. L., Ward P. A., Becker E. L. Inhibition of in vivo and in vitro neutrophil responses to chemotactic factors by a competitive antagonist. J Immunol. 1978 Apr;120(4):1326–1332. [PubMed] [Google Scholar]
  33. RAPP H. J., BORSOS T. EFFECTS OF LOW IONIC STRENGTH ON IMMUNE HEMOLYSIS. J Immunol. 1963 Dec;91:826–832. [PubMed] [Google Scholar]
  34. Samuelsson B., Granström E., Green K., Hamberg M., Hammarström S. Prostaglandins. Annu Rev Biochem. 1975;44:669–695. doi: 10.1146/annurev.bi.44.070175.003321. [DOI] [PubMed] [Google Scholar]
  35. Schiffmann E., Corcoran B. A., Wahl S. M. N-formylmethionyl peptides as chemoattractants for leucocytes. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1059–1062. doi: 10.1073/pnas.72.3.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Showell H. J., Freer R. J., Zigmond S. H., Schiffmann E., Aswanikumar S., Corcoran B., Becker E. L. The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils. J Exp Med. 1976 May 1;143(5):1154–1169. doi: 10.1084/jem.143.5.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. 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]

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