Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1991 Sep;59(9):3046–3052. doi: 10.1128/iai.59.9.3046-3052.1991

Regulation of leukotriene B4 generation from human polymorphonuclear granulocytes after stimulation with formyl-methionyl-leucyl phenylalanine: effects of pertussis and cholera toxins.

T Hensler 1, M Köller 1, W König 1
PMCID: PMC258133  PMID: 1652558

Abstract

The effects of holotoxins and toxin subunits from Bordetella pertussis and Vibrio cholerae strains on intact and digitonin-permeabilized human polymorphonuclear neutrophils were studied. Our data clearly demonstrate that formyl-methionyl-leucyl-phenylalanine (fMLP)-induced generation of chemotactic active leukotriene B4 was inhibited by both holotoxins as well as by their isolated enzymatic A protomers. In contrast, the respective binding components (B oligomers) did not affect leukotriene formation. Priming of digitonin-permeabilized neutrophils with either guanylylimidodiphosphate or inositol trisphosphate increased subsequent stimulation with fMLP. In contrast, diacylglycerol decreased fMLP-induced leukotriene B4 formation, but inositol trisphosphate and diacylglycerol had no effect on inhibition mediated by the toxins. In addition, pertussis and cholera toxins reduced the specific binding of [3H]fMLP. Scatchard plot analysis revealed that the observed decrease of peptide binding was due to a reduced number of receptor sites. The fMLP-stimulated [3H]guanylylimidodiphosphate binding and GTPase activity used as parameters for the activation of G proteins were decreased in parallel. These results suggest altered chemotactic receptor numbers and G-protein functions responsible for the toxin-dependent suppression of fMLP-mediated response for neutrophils.

Full text

PDF
3046

Selected References

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

  1. Ali H., Collado-Escobar D. M., Beaven M. A. The rise in concentration of free Ca2+ and of pH provides sequential, synergistic signals for secretion in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells. J Immunol. 1989 Oct 15;143(8):2626–2633. [PubMed] [Google Scholar]
  2. Andersson T., Dahlgren C., Lew P. D., Stendahl O. Cell surface expression of fMet-Leu-Phe receptors on human neutrophils. Correlation to changes in the cytosolic free Ca2+ level and action of phorbol myristate acetate. J Clin Invest. 1987 Apr;79(4):1226–1233. doi: 10.1172/JCI112941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bauldry S. A., Wykle R. L., Bass D. A. Phospholipase A2 activation in human neutrophils. Differential actions of diacylglycerols and alkylacylglycerols in priming cells for stimulation by N-formyl-Met-Leu-Phe. J Biol Chem. 1988 Nov 15;263(32):16787–16795. [PubMed] [Google Scholar]
  4. Becker E. L., Kanaho Y., Kermode J. C. Nature and functioning of the pertussis toxin-sensitive G protein of neutrophils. Biomed Pharmacother. 1987;41(6):289–297. [PubMed] [Google Scholar]
  5. Berridge M. J. Inositol trisphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem. 1987;56:159–193. doi: 10.1146/annurev.bi.56.070187.001111. [DOI] [PubMed] [Google Scholar]
  6. Bray M. A. Leukotrienes in inflammation. Agents Actions. 1986 Oct;19(1-2):87–99. doi: 10.1007/BF01977263. [DOI] [PubMed] [Google Scholar]
  7. Brom J., Schönfeld W., König W. Metabolism of leukotriene B4 by activated human polymorphonuclear granulocytes. Immunology. 1988 Jul;64(3):509–518. [PMC free article] [PubMed] [Google Scholar]
  8. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  9. Cockcroft S., Stutchfield J. The receptors for ATP and fMetLeuPhe are independently coupled to phospholipases C and A2 via G-protein(s). Relationship between phospholipase C and A2 activation and exocytosis in HL60 cells and human neutrophils. Biochem J. 1989 Nov 1;263(3):715–723. doi: 10.1042/bj2630715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Conquer J., Mahadevappa V. G. Inhibition of protein kinase C by H-7 potentiates the release of oleic, linoleic and arachidonic acids in A23187-stimulated human neutrophils. Biochem Biophys Res Commun. 1990 Feb 28;167(1):168–173. doi: 10.1016/0006-291x(90)91746-f. [DOI] [PubMed] [Google Scholar]
  11. Gilman A. G. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–649. doi: 10.1146/annurev.bi.56.070187.003151. [DOI] [PubMed] [Google Scholar]
  12. Gray L. S., Huber K. S., Gray M. C., Hewlett E. L., Engelhard V. H. Pertussis toxin effects on T lymphocytes are mediated through CD3 and not by pertussis toxin catalyzed modification of a G protein. J Immunol. 1989 Mar 1;142(5):1631–1638. [PubMed] [Google Scholar]
  13. Hansson G., Lindgren J. A., Dahlén S. E., Hedqvist P., Samuelsson B. Identification and biological activity of novel omega-oxidized metabolites of leukotriene B4 from human leukocytes. FEBS Lett. 1981 Jul 20;130(1):107–112. doi: 10.1016/0014-5793(81)80676-x. [DOI] [PubMed] [Google Scholar]
  14. Hensler T., Raulf M., Megret F., Alouf J. E., König W. Modulation of leukotriene generation by pertussis toxin. Infect Immun. 1989 Oct;57(10):3165–3171. doi: 10.1128/iai.57.10.3165-3171.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Knöller J., Schönfeld W., Köller M., Hensler T., König W. Arachidonic acid metabolites from polymorphonuclear leukocytes of healthy donors, severely burned patients and children with cystic fibrosis--routine monitoring by high-performance liquid chromatography. J Chromatogr. 1988 Jun 3;427(2):199–208. doi: 10.1016/0378-4347(88)80122-1. [DOI] [PubMed] [Google Scholar]
  16. Koo C., Lefkowitz R. J., Snyderman R. Guanine nucleotides modulate the binding affinity of the oligopeptide chemoattractant receptor on human polymorphonuclear leukocytes. J Clin Invest. 1983 Sep;72(3):748–753. doi: 10.1172/JCI111045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. König W., Schönfeld W., Raulf M., Köller M., Knöller J., Scheffer J., Brom J. The neutrophil and leukotrienes--role in health and disease. Eicosanoids. 1990;3(1):1–22. [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Matsumoto T., Molski T. F., Kanaho Y., Becker E. L., Sha'afi R. I. G-protein dissociation, GTP-GDP exchange and GTPase activity in control and PMA treated neutrophils stimulated by fMet-Leu-Phe. Biochem Biophys Res Commun. 1987 Mar 13;143(2):489–498. doi: 10.1016/0006-291x(87)91380-5. [DOI] [PubMed] [Google Scholar]
  20. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  21. Okajima F., Ui M. ADP-ribosylation of the specific membrane protein by islet-activating protein, pertussis toxin, associated with inhibition of a chemotactic peptide-induced arachidonate release in neutrophils. A possible role of the toxin substrate in Ca2+-mobilizing biosignaling. J Biol Chem. 1984 Nov 25;259(22):13863–13871. [PubMed] [Google Scholar]
  22. Prentki M., Wollheim C. B., Lew P. D. Ca2+ homeostasis in permeabilized human neutrophils. Characterization of Ca2+-sequestering pools and the action of inositol 1,4,5-triphosphate. J Biol Chem. 1984 Nov 25;259(22):13777–13782. [PubMed] [Google Scholar]
  23. Rosoff P. M., Walker R., Winberry L. Pertussis toxin triggers rapid second messenger production in human T lymphocytes. J Immunol. 1987 Oct 1;139(7):2419–2423. [PubMed] [Google Scholar]
  24. Rotrosen D., Leto T. L. Phosphorylation of neutrophil 47-kDa cytosolic oxidase factor. Translocation to membrane is associated with distinct phosphorylation events. J Biol Chem. 1990 Nov 15;265(32):19910–19915. [PubMed] [Google Scholar]
  25. Salari H., Braquet P., Naccache P., Borgeat P. Characterization of effect of N-formyl-methionyl-leucyl-phenylalanine on leukotriene synthesis in human polymorphonuclear leukocytes. Inflammation. 1985 Jun;9(2):127–138. doi: 10.1007/BF00917585. [DOI] [PubMed] [Google Scholar]
  26. Sklar L. A., Bokoch G. M., Button D., Smolen J. E. Regulation of ligand-receptor dynamics by guanine nucleotides. Real-time analysis of interconverting states for the neutrophil formyl peptide receptor. J Biol Chem. 1987 Jan 5;262(1):135–139. [PubMed] [Google Scholar]
  27. Sommermeyer H., Resch K. Pertussis toxin B-subunit-induced Ca2(+)-fluxes in Jurkat human lymphoma cells: the action of long-term pre-treatment with cholera and pertussis holotoxins. Cell Signal. 1990;2(2):115–128. doi: 10.1016/0898-6568(90)90015-3. [DOI] [PubMed] [Google Scholar]
  28. Verghese M., Uhing R. J., Snyderman R. A pertussis/choleratoxin-sensitive N protein may mediate chemoattractant receptor signal transduction. Biochem Biophys Res Commun. 1986 Jul 31;138(2):887–894. doi: 10.1016/s0006-291x(86)80579-4. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES