Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Mar;105(3):756–762. doi: 10.1111/j.1476-5381.1992.tb09051.x

Platelet-activating factor (PAF) plays an important role in the immediate asthmatic response in guinea-pig by augmenting the response to histamine.

S Morooka 1, M Uchida 1, N Imanishi 1
PMCID: PMC1908441  PMID: 1628161

Abstract

1. To investigate the role of platelet activating factor (PAF) in the immediate asthmatic response, we examined the bronchial reactivity to histamine after administration of PAF to guinea-pigs or antigen challenge to passively sensitized guinea-pigs. 2. A bolus injection of PAF (20-40 ng kg-1), which did not cause a significant increase in intrathoracic pressure (ITP), augmented the bronchial response to histamine almost 8 fold. This airway hyperreactivity was observed even 1 min after PAF treatment. 3. A subthreshold dose of antigen (0.01 mg kg-1, i.v.) also provoked hyperreactivity to histamine, which became significant 6 and 11 min after the antigen treatment. 4. The specific PAF-antagonists, SM-10661 and CV-6209 (i.v.) dose-dependently inhibited both PAF- and antigen-induced airway hyperreactivities to histamine. 5. These results suggest that PAF plays an important role in antigen-induced acute airway responses by augmenting the activities of spasmogens.

Full text

PDF
756

Selected References

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

  1. Anderson G. P., White H. L., Fennessy M. R. Increased airways responsiveness to histamine induced by platelet activating factor in the guinea-pig: possible role of lipoxygenase metabolites. Agents Actions. 1988 Jun;24(1-2):1–7. doi: 10.1007/BF01968073. [DOI] [PubMed] [Google Scholar]
  2. Bussolino F., Breviario F., Tetta C., Aglietta M., Mantovani A., Dejana E. Interleukin 1 stimulates platelet-activating factor production in cultured human endothelial cells. J Clin Invest. 1986 Jun;77(6):2027–2033. doi: 10.1172/JCI112532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Christman B. W., Lefferts P. L., Snapper J. R. Effect of platelet-activating factor on aerosol histamine responsiveness in awake sheep. Am Rev Respir Dis. 1987 Jun;135(6):1267–1270. doi: 10.1164/arrd.1987.135.6.1267. [DOI] [PubMed] [Google Scholar]
  4. Chung K. F., Aizawa H., Leikauf G. D., Ueki I. F., Evans T. W., Nadel J. A. Airway hyperresponsiveness induced by platelet-activating factor: role of thromboxane generation. J Pharmacol Exp Ther. 1986 Mar;236(3):580–584. [PubMed] [Google Scholar]
  5. Cockcroft D. W. Mechanism of perennial allergic asthma. Lancet. 1983 Jul 30;2(8344):253–256. doi: 10.1016/s0140-6736(83)90235-0. [DOI] [PubMed] [Google Scholar]
  6. Cockcroft D. W., Ruffin R. E., Dolovich J., Hargreave F. E. Allergen-induced increase in non-allergic bronchial reactivity. Clin Allergy. 1977 Nov;7(6):503–513. doi: 10.1111/j.1365-2222.1977.tb01481.x. [DOI] [PubMed] [Google Scholar]
  7. Coyle A. J., Page C. P., Atkinson L., Sjoerdsma K., Touvay C., Metzger W. J. Modification of allergen-induced airway obstruction and airway hyperresponsiveness in an allergic rabbit model by the selective platelet-activating factor antagonist, BN 52021. J Allergy Clin Immunol. 1989 Dec;84(6 Pt 1):960–967. doi: 10.1016/0091-6749(89)90395-3. [DOI] [PubMed] [Google Scholar]
  8. Coyle A. J., Urwin S. C., Page C. P., Touvay C., Villain B., Braquet P. The effect of the selective PAF antagonist BN 52021 on PAF- and antigen-induced bronchial hyper-reactivity and eosinophil accumulation. Eur J Pharmacol. 1988 Mar 22;148(1):51–58. doi: 10.1016/0014-2999(88)90453-0. [DOI] [PubMed] [Google Scholar]
  9. Cuss F. M., Dixon C. M., Barnes P. J. Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man. Lancet. 1986 Jul 26;2(8500):189–192. doi: 10.1016/s0140-6736(86)92489-x. [DOI] [PubMed] [Google Scholar]
  10. Dewar A., Archer C. B., Paul W., Page C. P., MacDonald D. M., Morley J. Cutaneous and pulmonary histopathological responses to platelet activating factor (Paf-acether) in the guinea-pig. J Pathol. 1984 Sep;144(1):25–34. doi: 10.1002/path.1711440104. [DOI] [PubMed] [Google Scholar]
  11. Durham S. R., Kay A. B. Eosinophils, bronchial hyperreactivity and late-phase asthmatic reactions. Clin Allergy. 1985 Sep;15(5):411–418. doi: 10.1111/j.1365-2222.1985.tb02290.x. [DOI] [PubMed] [Google Scholar]
  12. Fitzgerald M. F., Moncada S., Parente L. The anaphylactic release of platelet-activating factor from perfused guinea-pig lungs. Br J Pharmacol. 1986 May;88(1):149–153. doi: 10.1111/j.1476-5381.1986.tb09481.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Havill A. M., Van Valen R. G., Handley D. A. Prevention of non-specific airway hyperreactivity after allergen challenge in guinea-pigs by the PAF receptor antagonist SDZ 64-412. Br J Pharmacol. 1990 Feb;99(2):396–400. doi: 10.1111/j.1476-5381.1990.tb14715.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hwang S. B. Identification of a second putative receptor of platelet-activating factor from human polymorphonuclear leukocytes. J Biol Chem. 1988 Mar 5;263(7):3225–3233. [PubMed] [Google Scholar]
  15. Komuro Y., Imanishi N., Uchida M., Morooka S. Biological effect of orally active platelet-activating factor receptor antagonist SM-10661. Mol Pharmacol. 1990 Sep;38(3):378–384. [PubMed] [Google Scholar]
  16. Lellouch-Tubiana A., Lefort J., Pirotzky E., Vargaftig B. B., Pfister A. Ultrastructural evidence for extravascular platelet recruitment in the lung upon intravenous injection of platelet-activating factor (PAF-acether) to guinea-pigs. Br J Exp Pathol. 1985 Jun;66(3):345–355. [PMC free article] [PubMed] [Google Scholar]
  17. Lellouch-Tubiana A., Lefort J., Simon M. T., Pfister A., Vargaftig B. B. Eosinophil recruitment into guinea pig lungs after PAF-acether and allergen administration. Modulation by prostacyclin, platelet depletion, and selective antagonists. Am Rev Respir Dis. 1988 Apr;137(4):948–954. doi: 10.1164/ajrccm/137.4.948. [DOI] [PubMed] [Google Scholar]
  18. Mencia-Huerta J. M., Lewis R. A., Razin E., Austen K. F. Antigen-initiated release of platelet-activating factor (PAF-acether) from mouse bone marrow-derived mast cells sensitized with monoclonal IgE. J Immunol. 1983 Dec;131(6):2958–2964. [PubMed] [Google Scholar]
  19. Morley J., Sanjar S., Page C. P. The platelet in asthma. Lancet. 1984 Nov 17;2(8412):1142–1144. doi: 10.1016/s0140-6736(84)91567-8. [DOI] [PubMed] [Google Scholar]
  20. Patterson R., Harris K. E., Handley D. A., Saunders R. N. Evaluation of the effect of a platelet activating factor antagonist on platelet activating factor and Ascaris antigen-induced airway responses in rhesus monkeys. J Lab Clin Med. 1987 Nov;110(5):606–611. [PubMed] [Google Scholar]
  21. Popa V., Douglas J. S., Bouhuys A. Airway responses to histamine, acetylcholine, and propranolol in anaphylactic hypersensitivity in guinea pigs. J Allergy Clin Immunol. 1973 Jun;51(6):344–356. doi: 10.1016/0091-6749(73)90073-0. [DOI] [PubMed] [Google Scholar]
  22. Rubin A. H., Smith L. J., Patterson R. The bronchoconstrictor properties of platelet-activating factor in humans. Am Rev Respir Dis. 1987 Nov;136(5):1145–1151. doi: 10.1164/ajrccm/136.5.1145. [DOI] [PubMed] [Google Scholar]
  23. Sanjar S., Aoki S., Boubekeur K., Burrows L., Colditz I., Chapman I., Morley J. Inhibition of PAF-induced eosinophil accumulation in pulmonary airways of guinea pigs by anti-asthma drugs. Jpn J Pharmacol. 1989 Oct;51(2):167–172. doi: 10.1254/jjp.51.167. [DOI] [PubMed] [Google Scholar]
  24. Stewart A. G., Dubbin P. N., Harris T., Dusting G. J. 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. 1990 Apr;87(8):3215–3219. doi: 10.1073/pnas.87.8.3215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stewart A. G., Dusting G. J. Characterization of receptors for platelet-activating factor on platelets, polymorphonuclear leukocytes and macrophages. Br J Pharmacol. 1988 Aug;94(4):1225–1233. doi: 10.1111/j.1476-5381.1988.tb11642.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Terashita Z., Imura Y., Takatani M., Tsushima S., Nishikawa K. CV-6209, a highly potent antagonist of platelet activating factor in vitro and in vivo. J Pharmacol Exp Ther. 1987 Jul;242(1):263–268. [PubMed] [Google Scholar]
  27. Tomioka K., Garrido R., Ahmed A., Stevenson J. S., Abraham W. M. YM461, a PAF antagonist, blocks antigen-induced late airway responses and airway hyperresponsiveness in allergic sheep. Eur J Pharmacol. 1989 Nov 7;170(3):209–215. doi: 10.1016/0014-2999(89)90541-4. [DOI] [PubMed] [Google Scholar]
  28. 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]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES