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. 1992 Dec;107(4):1029–1036. doi: 10.1111/j.1476-5381.1992.tb13402.x

Guinea-pig treatment with pertussis toxin suppresses macrophage-dependent bronchoconstriction by fMLP and fails to inhibit the effects of PAF.

C Kadiri 1, D Leduc 1, J Lefort 1, A Imaizumi 1, B B Vargaftig 1
PMCID: PMC1907936  PMID: 1334747

Abstract

1. Bronchoconstriction and thromboxane B2 (TxB2) release following the intra-tracheal administration of the secretagogue N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to lungs from pertussis toxin-treated guinea-pigs in vivo and in vitro were inhibited as compared to saline-treated animals, under conditions where the responses to PAF were modified less effectively. 2. The cell target accounting for bronchoconstriction by fMLP and for inhibition by pertussis toxin is located in the airways and is probably the alveolar macrophage. Indeed (a) fMLP-induced superoxide anions and TxB2 formation by alveolar macrophages were inhibited by pertussis toxin given in vivo; (b) Gi proteins of membranes from alveolar macrophages were ADP-ribosylated in vivo by pertussis toxin and (c) bronchoconstriction and TxB2 release in response to the intra-tracheal administration of fMLP to lungs from pertussis toxin-treated animals were restored when alveolar macrophages from control guinea-pigs were transferred into the airways of pertussis toxin-treated animals before lung isolation. 3. Pertussis toxin administered to guinea-pigs in vivo, reduced the subsequent TxB2 formation and superoxide anion release by alveolar macrophages stimulated with PAF, but failed to inhibit PAF-induced bronchoconstriction. 4. Formation of TxB2 by alveolar macrophages following the intra-tracheal administration of fMLP accounts for bronchoconstriction and requires pertussis toxin-sensitive Gi proteins. PAF operates via a different mechanism, which is independent of Gi-like protein and involves mediators other than TxB2 and superoxide anions.

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Selected References

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

  1. Bachelet M., Masliah J., Malanchere E., Lefort J., Bereziat G., Vargaftig B. B. Reduced responsiveness of bronchoalveolar cells from sensitised guinea-pigs to the cyclic AMP--stimulating effect of prostaglandin E2 and beta-adrenoceptor agonists. Pulm Pharmacol. 1989;2(1):41–44. doi: 10.1016/s0952-0600(89)80008-0. [DOI] [PubMed] [Google Scholar]
  2. Boukili M. A., Bureau M. F., Lellouch-Tubiana A., Lefort J., Simon M. T., Vargaftig B. B. Alveolar macrophages and eicosanoids but not neutrophils, mediate bronchoconstriction induced by FMLP in the guinea-pig. Br J Pharmacol. 1989 Sep;98(1):61–70. doi: 10.1111/j.1476-5381.1989.tb16863.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boukili M. A., Bureau M., Lagente V., Lefort J., Lellouch-Tubiana A., Malanchère E., Vargaftig B. B. Pharmacological modulation of the effects of N-formyl-L-methionyl-L-leucyl-L-phenylalanine in guinea-pigs: involvement of the arachidonic acid cascade. Br J Pharmacol. 1986 Oct;89(2):349–359. doi: 10.1111/j.1476-5381.1986.tb10267.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  5. Braquet P., Touqui L., Shen T. Y., Vargaftig B. B. Perspectives in platelet-activating factor research. Pharmacol Rev. 1987 Jun;39(2):97–145. [PubMed] [Google Scholar]
  6. Bureau M. F., De Clerck F., Lefort J., Arreto C. D., Vargaftig B. B. Thromboxane A2 accounts for bronchoconstriction but not for platelet sequestration and microvascular albumin exchanges induced by fMLP in the guinea pig lung. J Pharmacol Exp Ther. 1992 Feb;260(2):832–840. [PubMed] [Google Scholar]
  7. Cailla H. L., Cros G. S., Jolu E. J., Delaage M. A., Depieds R. C. Comparison between rat and rabbit anticyclic AMP antibodies--specificity toward acyl derivatives of cyclic AMP. Anal Biochem. 1973 Dec;56(2):383–393. doi: 10.1016/0003-2697(73)90204-2. [DOI] [PubMed] [Google Scholar]
  8. Chang F. H., Bourne H. R. Cholera toxin induces cAMP-independent degradation of Gs. J Biol Chem. 1989 Apr 5;264(10):5352–5357. [PubMed] [Google Scholar]
  9. Crouch M. F., Lapetina E. G. A role for Gi in control of thrombin receptor-phospholipase C coupling in human platelets. J Biol Chem. 1988 Mar 5;263(7):3363–3371. [PubMed] [Google Scholar]
  10. Fu T., Okano Y., Nozawa Y. Bradykinin-induced generation of inositol 1,4,5-trisphosphate in fibroblasts and neuroblastoma cells: effect of pertussis toxin, extracellular calcium, and down-regulation of protein kinase C. Biochem Biophys Res Commun. 1988 Dec 30;157(3):1429–1435. doi: 10.1016/s0006-291x(88)81035-0. [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. Gilman A. G. The Albert Lasker Medical Awards. G proteins and regulation of adenylyl cyclase. JAMA. 1989 Oct 6;262(13):1819–1825. [PubMed] [Google Scholar]
  13. Hayaishi O., Ueda K. Poly(ADP-ribose) and ADP-ribosylation of proteins. Annu Rev Biochem. 1977;46:95–116. doi: 10.1146/annurev.bi.46.070177.000523. [DOI] [PubMed] [Google Scholar]
  14. Hescheler J., Rosenthal W., Trautwein W., Schultz G. The GTP-binding protein, Go, regulates neuronal calcium channels. 1987 Jan 29-Feb 4Nature. 325(6103):445–447. doi: 10.1038/325445a0. [DOI] [PubMed] [Google Scholar]
  15. Homma Y., Hashimoto T., Nagai Y., Takenawa T. Evidence for differential activation of arachidonic acid metabolism in formylpeptide- and macrophage-activation-factor-stimulated guinea-pig macrophages. Biochem J. 1985 Aug 1;229(3):643–651. doi: 10.1042/bj2290643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Horn W., Karnovsky M. L. Features of the translocation of protein kinase C in neutrophils stimulated with the chemotactic peptide f-Met-Leu-Phe. Biochem Biophys Res Commun. 1986 Sep 30;139(3):1169–1175. doi: 10.1016/s0006-291x(86)80300-x. [DOI] [PubMed] [Google Scholar]
  17. Iiri T., Tohkin M., Morishima N., Ohoka Y., Ui M., Katada T. Chemotactic peptide receptor-supported ADP-ribosylation of a pertussis toxin substrate GTP-binding protein by cholera toxin in neutrophil-type HL-60 cells. J Biol Chem. 1989 Dec 15;264(35):21394–21400. [PubMed] [Google Scholar]
  18. Imaizumi A., Lefort J., Leduc D., Lellouch-Tubiana A., Vargaftig B. B. Pertussis toxin induces bronchopulmonary hyperresponsiveness in guinea-pigs while antagonizing the effects of formyl-L-methionyl-L-leucyl-L-phenylalanine. Eur J Pharmacol. 1992 Mar 3;212(2-3):177–186. doi: 10.1016/0014-2999(92)90327-z. [DOI] [PubMed] [Google Scholar]
  19. Kadiri C., Cherqui G., Masliah J., Rybkine T., Etienne J., Béréziat G. Mechanism of N-formyl-methionyl-leucyl-phenylalanine- and platelet-activating factor-induced arachidonic acid release in guinea pig alveolar macrophages: involvement of a GTP-binding protein and role of protein kinase A and protein kinase C. Mol Pharmacol. 1990 Sep;38(3):418–425. [PubMed] [Google Scholar]
  20. Kadiri C., Masliah J., Bachelet M., Vargaftig B. B., Béréziat G. Phospholipase A2-mediated release of arachidonic acid in stimulated guinea pig alveolar macrophages: interaction with lipid mediators and cyclic AMP. J Cell Biochem. 1989 Jun;40(2):157–164. doi: 10.1002/jcb.240400204. [DOI] [PubMed] [Google Scholar]
  21. Kikuchi A., Kozawa O., Kaibuchi K., Katada T., Ui M., Takai Y. Direct evidence for involvement of a guanine nucleotide-binding protein in chemotactic peptide-stimulated formation of inositol bisphosphate and trisphosphate in differentiated human leukemic (HL-60) cells. Reconstitution with Gi or Go of the plasma membranes ADP-ribosylated by pertussis toxin. J Biol Chem. 1986 Sep 5;261(25):11558–11562. [PubMed] [Google Scholar]
  22. Krzanowski J. J., Polson J. B., Szentivanyi A. Pulmonary patterns of adenosine-3', 5'-cyclic monophosphate accumulations in response to adrenergic or histamine stimulation in Bordetella pertussis-sensitized mice. Biochem Pharmacol. 1976 Jul 15;25(14):1631–1637. doi: 10.1016/0006-2952(76)90475-5. [DOI] [PubMed] [Google Scholar]
  23. Lad P. M., Olson C. V., Smiley P. A. Association of the N-formyl-Met-Leu-Phe receptor in human neutrophils with a GTP-binding protein sensitive to pertussis toxin. Proc Natl Acad Sci U S A. 1985 Feb;82(3):869–873. doi: 10.1073/pnas.82.3.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lefort J., Rotilio D., Vargaftig B. B. The platelet-independent release of thromboxane A2 by Paf-acether from guinea-pig lungs involves mechanisms distinct from those for leukotriene. Br J Pharmacol. 1984 Jul;82(3):565–575. doi: 10.1111/j.1476-5381.1984.tb10795.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Naccache P. H., Molski M. M., Volpi M., Becker E. L., Sha'afi R. I. Unique inhibitory profile of platelet activating factor induced calcium mobilization, polyphosphoinositide turnover and granule enzyme secretion in rabbit neutrophils towards pertussis toxin and phorbol ester. Biochem Biophys Res Commun. 1985 Jul 31;130(2):677–684. doi: 10.1016/0006-291x(85)90470-x. [DOI] [PubMed] [Google Scholar]
  26. Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. O'Flaherty J. T., Nishihira J. Arachidonate metabolites, platelet-activating factor, and the mobilization of protein kinase C in human polymorphonuclear neutrophils. J Immunol. 1987 Mar 15;138(6):1889–1895. [PubMed] [Google Scholar]
  28. Polakis P. G., Uhing R. J., Snyderman R. The formylpeptide chemoattractant receptor copurifies with a GTP-binding protein containing a distinct 40-kDa pertussis toxin substrate. J Biol Chem. 1988 Apr 5;263(10):4969–4976. [PubMed] [Google Scholar]
  29. Prpic V., Uhing R. J., Weiel J. E., Jakoi L., Gawdi G., Herman B., Adams D. O. Biochemical and functional responses stimulated by platelet-activating factor in murine peritoneal macrophages. J Cell Biol. 1988 Jul;107(1):363–372. doi: 10.1083/jcb.107.1.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schlondorff D., Singhal P., Hassid A., Satriano J. A., DeCandido S. Relationship of GTP-binding proteins, phospholipase C, and PGE2 synthesis in rat glomerular mesangial cells. Am J Physiol. 1989 Jan;256(1 Pt 2):F171–F178. doi: 10.1152/ajprenal.1989.256.1.F171. [DOI] [PubMed] [Google Scholar]
  31. Sors H., Pradelles P., Dray F., Rigaud M., Maclouf J., Bernard P. Analytical methods for thromboxane B2 measurement and validation of radioimmunoassay by gas liquid chromatography-mass spectrometry. Prostaglandins. 1978 Aug;16(2):277–290. doi: 10.1016/0090-6980(78)90030-8. [DOI] [PubMed] [Google Scholar]
  32. Vadas M. A., David J. R., Butterworth A., Pisani N. T., Siongok T. A. A new method for the purification of human eosinophils and neutrophils, and a comparison of the ability of these cells to damage schistosomula of Schistosoma mansoni. J Immunol. 1979 Apr;122(4):1228–1236. [PubMed] [Google Scholar]
  33. Vargaftig B. B., Lefort J., Chignard M., Benveniste J. Platelet-activating factor induces a platelet-dependent bronchoconstriction unrelated to the formation of prostaglandin derivatives. Eur J Pharmacol. 1980 Jul 25;65(2-3):185–192. doi: 10.1016/0014-2999(80)90391-x. [DOI] [PubMed] [Google Scholar]
  34. Yamamoto K., Tanimoto T., Kim S., Kikuchi A., Takai Y. Small molecular weight GTP-binding proteins and signal transduction. Clin Chim Acta. 1989 Dec 15;185(3):347–355. doi: 10.1016/0009-8981(89)90225-8. [DOI] [PubMed] [Google Scholar]

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