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Interactions between synthesis of platelet-activating factor and leukotriene B4 in isolated human polymorphonuclear leukocytes

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Abstract

The aim of the present work was to study interactions between the synthesis of platelet-activating factor (PAF) and leukotriene B4 (LTB4) in human polymorphonuclear leukocytes (PMNs) in vitro. PAF, at nanomolar concentrations, stimulated calcium ionophore A23187-activated PMNs to release LTB4 and 5-hydroxyeicosatetraenoic acid (5-HETE). This seems to be a receptor-mediated process as it was blocked by a PAF receptor antagonist WEB 2086 (IC50 6.6±3.9μM). Moreover, LTB4 stimulated the formation of PAF in activated PMNs. WEB 2086 did not, however, alter PMN migration towards either LTB4 or the chemotactic peptide FMLP. This suggests that the enhancement of PAF synthesis in response to LTB4 is a concomitant event rather than a mediating process in LTB4-induced chemotactic movement of PMNs. These effects are implicated in the complex network of interactions between inflammatory mediators that results accumulation and activation of PMNs in the exacerbation of inflammatory processes.

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References

  1. Bray, M. A. 1986. Leukotrienes in inflammation.Agents Actions 19:87–99.

    Google Scholar 

  2. Pinckard, R. N., J. C. Ludwig, andL. M. McManus. 1988. Platelet-activating factors.In Inflammation: Basic Principles and Clinical Correlates. J. I. Gallin, I. M. Goldstein, and R. Snyderman, editors. Raven Press, New York. 139–167.

    Google Scholar 

  3. König, W., W. Schönfeld, M. Raulf, M. Köller, J. Knöller, J. Scheffer, andJ. Brom. 1990. The neutrophil and leukotrienes—role in health and disease.Eicosanoids 3:1–22.

    Google Scholar 

  4. Koltai, M., D. Hosford, P. Guinot, A. Esanu, andP. Braquet. 1991. Platelet activating factor (PAF). A review of its effects, antagonists and possible future clinical implications (Part I).Drugs 42:9–29.

    Google Scholar 

  5. Chilton, F. H., M. Cluzel, andM. Triggiani. 1991. Recent advances in our understanding of the biochemical interactions between platelet-activating factor and arachidonic acid.Lipids 26:1021–1027.

    Google Scholar 

  6. Kubes, P., G. Ibbotson, J. Russell, J. L. Wallace, andD. N. Granger. 1990. Role of platelet-activating factor in ischemia/reperfusion-induced leukocyte adherence.Am. J. Physiol. 259:G300-G305.

    Google Scholar 

  7. Stewart, A. G., P. N. Dubbin, T. Harris, andG. J. Dusting. 1990. Platelet-activating factor may act as a second messenger in the release of icosanoids and superoxide anions from leukocytes and endothelial cells.Proc. Natl. Acad. Sci. U.S.A. 87:3215–3219.

    Google Scholar 

  8. van der Zee, H., D. G. Moon, J. E. Kaplan, P. W. Gudewicz, andJ. Fenton, II. 1991. Thrombin-induced leukopenia and thrombocytopenia are attenuated by PAF antagonist WEB 2086.J. Lab. Clin. Med. 117:305–312.

    Google Scholar 

  9. Bøyum, A. 1976. Isolation of lymphocytes, granulocytes and macrophages.Scand. J. Immunol. 5(Suppl.):9–15.

    Google Scholar 

  10. Moilanen, E., J. Alanko, E. Seppälä, andH. Vapaatalo. 1988. Effects of antirheumatic drugs on leukotriene B4 and prostanoid synthesis in human polymorphonuclear leukocytes in vitro.Agents Actions 24:387–394.

    Google Scholar 

  11. Casals-Stenzel, J., G. Muacevic, andK-H. Weber. 1987. Pharmacological actions of WEB 2086, a new specific antagonist of platelet activating factor.J. Pharmacol. Exp. Ther. 241:974–981.

    Google Scholar 

  12. Radin, N. S. 1981. Extraction of tissue lipids with a solvent of low toxicity.Methods Enzymol. 72:5–7.

    Google Scholar 

  13. Grandel, K. E., R. S. Farr, A. A. Wanderer, T. C. Eisenstadt, andS. I. Wasserman. 1985. Association of platelet-activating factor with primary acquired cold urticaria.N. Engl. J. Med. 313:405–409.

    Google Scholar 

  14. Henson, P. M. 1976. Activation and desensitization of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. I. Characteristics of the secretory response.J. Exp. Med. 143:937–951.

    Google Scholar 

  15. Chang, S.-W., C. O. Feddersen, P. M. Henson, andN. F. Voelkel. 1987. Platelet-activating factor mediates hemodynamic changes and lung injury in endotoxin-treated rats.J. Clin. Invest. 79:1498–1509.

    Google Scholar 

  16. Gallin, J. I., R. A. Clark, andH. R. Kimball. 1973. Granulocyte chemotaxis: an improved in vitro assay employing51Cr-labeled granulocytes.J. Immunol. 110:233–240.

    Google Scholar 

  17. Kankaanranta, H., E. Moilanen, andH. Vapaatalo. 1991. Tolfenamic acid inhibits leukotriene B4-induced chemotaxis of polymorphonuclear leukocytes in vitro.Inflammation 15:137–143.

    Google Scholar 

  18. Zimmerman, G. A., T. M. McIntyre, M. Mehra, andS. M. Prescott. 1990. Endothelial cell-associated platelet-activating factor: a novel mechanism for signaling intercellular adhesion.J. Cell. Biol. 110:529–540.

    Google Scholar 

  19. Tool, A. T. J., A. J. Verhoeven, D. Roos, andL. Koenderman. 1989. Platelet-activating factor (PAF) acts as an intercellular messenger in the changes of cytosolic free Ca2+ in human neutrophils induced by opsonized particles.FEBS Lett. 259:209–212.

    Google Scholar 

  20. Dive, C., J. W. Watson, andP. Workman. 1991. Multiparametric flow cytometry of the modulation of tumor cell membrane permeability by developmental antitumor ether lipid SRI 62–834 in EMT6 mouse mammary tumor and HL-60 human promyelocytic leukemia cells.Cancer Res. 51:799–806.

    Google Scholar 

  21. Workman, P., J. Donaldson, andM. Lohmeyer. 1991. Platelet-activating factor (PAF) antagonist WEB 2086 does not modulate the cytotoxicity of PAF or antitumour alkyl lysophospholipids ET-18-O-methyl and SRI 62-834 in HL-60 promyelocytic leukaemia cells.Biochem. Pharmacol. 41:319–322.

    Google Scholar 

  22. Stewart, A. G., T. Harris, M. De Nichilo, andA. F. Lopez. 1991. Involvement of leukotriene B4 and platelet-activating factor in cytokine priming of human polymorphonuclear leucocytes.Immunology 72:206–212.

    Google Scholar 

  23. Chilton, F. H., J. T. O'Flaherty, C. E. Walsh, M. J. Thomas, R. L. Wykle, L. R. DeChatelet, andB. M. Waite. 1982. Platelet activating factor. Stimulation of the lipoxygenase pathway in polymorphonuclear leukocytes by 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine.J. Biol. Chem. 257:5402–5407.

    Google Scholar 

  24. Lin, A. H., D. R. Morton, andR. R. Gorman. 1982. Acetyl glyceryl ether phosphorylcholine stimulates leukotriene B4 synthesis in human polymorphonuclear leukocytes.J. Clin. Invest. 70:1058–1065.

    Google Scholar 

  25. Dubois, C., E. Bissonnette, andM. Rola-Pleszczynski. 1989. Platelet-activating factor (PAF) enhances tumor necrosis factor production by alveolar macrophages.J. Immunol. 143:964–970.

    Google Scholar 

  26. Nieminen, M. M., E. K. Moilanen, J-E. J. Nyholm, M. O. Koskinen, J. I. Karvonen, T. J. Metsä-Ketelä, andH. Vapaatalo. 1991. Platelet-activating factor impairs mucociliary transport and increases plasma leukotriene B4 in man.Eur. Respir. J. 4:551–560.

    Google Scholar 

  27. Nieminen, M. M., E. K. Moilanen, M. O. Koskinen, J. I. Karvonen, L. Tuomisto, T. Metsä-Ketelä, andH. Vapaatalo. 1992. Inhaled budesonide fails to inhibit the PAF-induced increase in plasma leukotriene B4 in man.Br. J. Clin. Pharmacol. 33:645–652.

    Google Scholar 

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Author notes

  1. H. Vapaatalo

    Present address: Department of Pharmacology and Toxicology, University of Helsinki, Helsinki, Finland

Authors and Affiliations

  1. Department of Biomedical Sciences, University of Tampere, Finland

    E. Moilanen, A. -L. Kirkkola, H. Kankaanranta, M. M. Nieminen & H. Vapaatalo

  2. Departments of Clinical Pharmacology and Pulmonary Diseases, Tampere University Hospital, Tampere, Finland

    E. Moilanen, A. -L. Kirkkola, H. Kankaanranta, M. M. Nieminen & H. Vapaatalo

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  3. H. Kankaanranta
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  4. M. M. Nieminen
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  5. H. Vapaatalo
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Moilanen, E., Kirkkola, A.L., Kankaanranta, H. et al. Interactions between synthesis of platelet-activating factor and leukotriene B4 in isolated human polymorphonuclear leukocytes. Inflammation 17, 705–714 (1993). https://doi.org/10.1007/BF00920475

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