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Platelet Activating Factor as a Mediator and Therapeutic Approach in Bronchial Asthma

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Abstract

Platelet activating factor (PAF) is a potent phospholipid mediator involved in anaphylaxis and chronic inflammatory disorders, including bronchial asthma. PAF is able to act both, directly as a chemotactic factor and indirectly through the release of other inflammatory agents. Apart from its known potent ability to activate platelets, PAF influences other immune and inflammatory cells function involved in asthma, which may be of importance in the pathogenesis of the disease. In addition, PAF administration can mimic some of abnormalities observed in asthma, including bronchoconstriction, bronchial hyper responsiveness, and gas exchange impairment, which may be mediated by leukotrienes acting as secondary mediators of some PAF effects. Therefore, there has been an extensive interest in the role of PAF in human asthma and major efforts have been continued to discover drugs acting thorough inhibition of PAF effects in the disease. Surprisingly, PAF receptor antagonists have not clearly proven their clinical benefits. It may appear that the combined blockage of PAF effects and other mediators involved in asthma is a way to improve clinical efficacy and also an interesting approach to control inflammation in the disease. This review will focus on two main issues: the role of PAF and PAF antagonists in asthma.

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References

  1. Barnes, P. J., K. F. Chung, and C. P. Page. 1998. Inflammatory mediators of asthma: an update. Pharmacol. Rev. 50:515–596.

    PubMed  CAS  Google Scholar 

  2. Kay, A. B.. 1983. Mediators of hypersensitivity and inflammatory cells in the pathogenesis of bronchial asthma. Eur. J. Respir. Dis. Suppl. 129:1–44.

    PubMed  CAS  Google Scholar 

  3. Morley, J., and D. Wiesinger. 1986. Bronchial hyper-reactivity: recent preclinical developments. Allerg. Immunol. (Paris) 18:33–34 36.

    CAS  Google Scholar 

  4. Denjean, A., B. Arnoux, J. Benveniste, A. Lockhart, and R. Masse. 1981. Bronchoconstriction induced by intratracheal administration of platelet-activating factor (PAF-acether) in baboons. Agents Actions 11:567–568.

    Article  PubMed  CAS  Google Scholar 

  5. Zhu, T., F. Gobeil, A. Vazquez-Tello, M. Leduc, L. Rihakova, M. Bossolasco, G. Bkaily, K. Peri, D. R. Varma, R. Orvoine, and S. Chemtob. 2006. Intracrine signaling through lipid mediators and their cognate nuclear G-protein-coupled receptors: a paradigm based on PGE2, PAF, and LPA1 receptors. Can. J. Physiol. Pharmacol. 84:377–391.

    Article  PubMed  CAS  Google Scholar 

  6. Hwang, S. B.. 1990. Specific receptors of platelet-activating factor, receptor heterogeneity, and signal transduction mechanisms. J. Lipid Mediat. 2:123–158.

    PubMed  CAS  Google Scholar 

  7. Ishii, S., and T. Shimizu. 2000. Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. Prog. Lipid Res. 39:41–82.

    Article  PubMed  CAS  Google Scholar 

  8. Simon, H. U., P. W. Tsao, K. A. Siminovitch, G. B. Mills, and K. Blaser. 1994. Functional platelet-activating factor receptors are expressed by monocytes and granulocytes but not by resting or activated T and B lymphocytes from normal individuals or patients with asthma. J. Immunol. 153:364–377.

    PubMed  CAS  Google Scholar 

  9. McFadden, R. G., M. A. Bishop, A. N. Caveney, and L. J. Fraher. 1995. Effect of platelet activating factor (PAF) on the migration of human lymphocytes. Thorax 50:265–269.

    PubMed  CAS  Google Scholar 

  10. Kishimoto, S., W. Shimadzu, T. Izumi, T. Shimizu, H. Sagara, T. Fukuda, S. Makino, T. Sugiura, and K. Waku. 1997. Comparison of platelet-activating factor receptor mRNA levels in peripheral blood eosinophils from normal subjects and atopic asthmatic patients. Int. Arch. Allergy Immunol. 114(Suppl):60–63.

    Article  PubMed  Google Scholar 

  11. Shirasaki, H., M. Nishikawa, I. M. Adcock, J. C. Mak, T. Sakamoto, T. Shimizu, and P. J. Barnes. 1994. Expression of platelet-activating factor receptor mRNA in human and guinea pig lung. Am. J. Respir. Cell Mol. Biol. 10:533–537.

    PubMed  CAS  Google Scholar 

  12. Golino, P., G. Ambrosio, M. Ragni, I. Pascucci, M. Triggiani, A. Oriente, J. McNatt, L. M. Buja, M. Condorelli, and M. Chiariello. 1993. Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation. Circulation 88:1205–1214.

    PubMed  CAS  Google Scholar 

  13. Okuda, Y., I. Tsuyuguchi, and A. Yamatodani. 1988. Histamine release from human leukocytes by platelet-activating factor. Int. Arch. Allergy Appl. Immunol. 85:341–345.

    PubMed  CAS  Google Scholar 

  14. Okuda, Y., H. Hattori, T. Takashima, A. Miyatake, A. Yamatodani, I. Tsuyuguchi, and S. Kishimoto. 1990. Basophil histamine release by platelet-activating factor in aspirin-sensitive subjects with asthma. J. Allergy Clin. Immunol. 86:548–553.

    Article  PubMed  CAS  Google Scholar 

  15. Nilsson, G., D. D. Metcalfe, and D. D. Taub. 2000. Demonstration that platelet-activating factor is capable of activating mast cells and inducing a chemotactic response. Immunology 99:314–319.

    Article  PubMed  CAS  Google Scholar 

  16. Ghosh, S. K., P. Rafferty, C. De-Vos, and K. R. Patel. 1993. Effect of cetirizine, a potent H1 antagonist, on platelet activating factor induced bronchoconstriction in asthma. Clin. Exp. Allergy 23:524–527.

    Article  PubMed  CAS  Google Scholar 

  17. Louis, R., T. Bury, J. L. Corhay, and M. Radermecker. 1993. No increase in plasma histamine during PAF-induced airway obstruction in allergic asthmatics. Chest 104:806–810.

    Article  PubMed  CAS  Google Scholar 

  18. Arnoux, B., E. Jouvin-Marche, A. Arnoux, and J. Benveniste. 1982. Release of PAF-acether from human blood monocytes. Agents Actions 12:713–716.

    Article  PubMed  CAS  Google Scholar 

  19. Wardlaw, A. J., R. Moqbel, O. Cromwell, and A. B. Kay. 1986. Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils. J. Clin. Invest. 78:1701–1706.

    Article  PubMed  CAS  Google Scholar 

  20. Casale, T. B., R. A. Erger, and M. M. Little. 1993. Platelet-activating factor-induced human eosinophil transendothelial migration: evidence for a dynamic role of the endothelium. Am. J. Respir. Cell Mol. Biol. 8:77–82.

    PubMed  CAS  Google Scholar 

  21. Shindo, K., K. Koide, and M. Fukumura. 1997. PAF-induced eosinophil chemotaxis increases during an asthmatic attack and is inhibited by prednisolone in vivo and in vitro. Biochem. Biophys. Res. Commun. 237:146–151.

    Article  PubMed  CAS  Google Scholar 

  22. Zoratti, E. M., J. B. Sedgwick, R. R. Vrtis, and W. W. Busse. 1991. The effect of platelet-activating factor on the generation of superoxide anion in human eosinophils and neutrophils. J. Allergy Clin. Immunol. 88:749–758.

    Article  PubMed  CAS  Google Scholar 

  23. Kroegel, C., T. Yukawa, G. Dent, P. Venge, K. F. Chung, and P. J. Barnes. 1989. Stimulation of degranulation from human eosinophils by platelet-activating factor. J. Immunol. 142:3518–3526.

    PubMed  CAS  Google Scholar 

  24. Bruynzeel, P. L., L. Koenderman, P. T. Kok, M. L. Hameling, and J. Verhagen. 1986. Platelet-activating factor (PAF-acether) induced leukotriene C4 formation and luminol dependent chemiluminescence by human eosinophils. Pharmacol. Res. Commun. 18(Suppl):61–69.

    Article  PubMed  Google Scholar 

  25. Shindo, K., K. Koide, Y. Hirai, M. Sumitomo, and M. Fukumura. 1996. Priming effect of platelet activating factor on leukotriene C4 from stimulated eosinophils of asthmatic patients. Thorax 51:155–158.

    PubMed  CAS  Google Scholar 

  26. Miyagawa, H., M. Nabe, R. J. Hopp, C. Okada, A. K. Bewtra, and G. Townley. 1992. The effect of WEB 2086 on PAF-induced eosinophil chemotaxis and LTC4 production from eosinophils. Agents Actions 37:39–43.

    Article  PubMed  CAS  Google Scholar 

  27. Mizuki, M., H. Komatsu, Y. Akiyama, S. Iwane, and T. Tsuda. 1999. Inhibition of eosinophil activation in bronchoalveolar lavage fluid from atopic asthmatics by Y-24180, an antagonist to platelet-activating factor. Life Sci. 65:2031–2039.

    Article  PubMed  CAS  Google Scholar 

  28. Shindo, K., K. Koide, and M. Fukumura. 1997. Enhancement of leukotriene B4 release in stimulated asthmatic neutrophils by platelet activating factor. Thorax 52:1024–1029.

    Article  PubMed  CAS  Google Scholar 

  29. Basran, G. S., C. P. Page, W. Paul, and J. Morley. 1984. Platelet-activating factor: a possible mediator of the dual response to allergen? Clin. Allergy 14:75–79.

    Article  PubMed  CAS  Google Scholar 

  30. Henocq, E., and B. B. Vargaftig. 1988. Skin eosinophilia in atopic patients. J. Allergy Clin. Immunol. 81:691–695.

    Article  PubMed  CAS  Google Scholar 

  31. Thivierge, M., and M. Rola-Pleszczynski. 1992. Platelet-activating factor enhances interleukin-6 production by alveolar macrophages. J. Allergy Clin. Immunol. 90:796–802.

    Article  PubMed  CAS  Google Scholar 

  32. Huang, Y. H., L. Schafer-Elinder, H. Owman, J. C. Lorentzen, J. Ronnelid, and J. Frostegard. 1996. Induction of IL-4 by platelet-activating factor. Clin. Exp. Immunol. 106:143–148.

    Article  PubMed  CAS  Google Scholar 

  33. Shan, L., Y. Nishimura, Y. Kotani, and M. Yokoyama. 1999. Platelet-activating factor increases the expression of metalloproteinase-9 in human bronchial epithelial cells. Eur. J. Pharmacol. 374:147–156.

    Article  PubMed  CAS  Google Scholar 

  34. Beer, J. H., B. Wuthrich, and A. von-Felten. 1995. Allergen exposure in acute asthma causes the release of platelet-activating factor (PAF) as demonstrated by the desensitization of platelets to PAF. Int. Arch. Allergy Immunol. 106:291–296.

    PubMed  CAS  Google Scholar 

  35. Chan-Yeung, M., S. Lam, H. Chan, K. S. Tse, and H. Salari. 1991. The release of platelet-activating factor into plasma during allergen-induced bronchoconstriction. J. Allergy Clin. Immunol. 87:667–673.

    Article  PubMed  CAS  Google Scholar 

  36. Burgers, J. A., P. L. Bruynzeel, H. J. Mengelers, J. Kreukniet, and J. W. Akkerman. 1993. Occupancy of platelet receptors for platelet-activating factor in asthmatic patients during an allergen-induced bronchoconstrictive reaction. J. Lipid Mediat. 7:135–149.

    PubMed  CAS  Google Scholar 

  37. Hsieh, K. H., and C. K. Ng. 1993. Increased plasma platelet-activating factor in children with acute asthmatic attacks and decreased in vivo and in vitro production of platelet-activating factor after immunotherapy. J. Allergy Clin. Immunol. 91:650–657.

    Article  PubMed  CAS  Google Scholar 

  38. Kurosawa, M., T. Yamashita, and F. Kurimoto. 1994. Increased levels of blood platelet-activating factor in bronchial asthmatic patients with active symptoms. Allergy 49:60–63.

    Article  PubMed  CAS  Google Scholar 

  39. Stenton, S. C., E. N. Court, W. P. Kingston, P. Goadby, C. A. Kelly, M. Duddridge, C. Ward, D. J. Hendrick, and E. H. Walters. 1990. Platelet-activating factor in bronchoalveolar lavage fluid from asthmatic subjects. Eur. Respir. J. 3:408–413.

    PubMed  CAS  Google Scholar 

  40. Tsukioka, K., M. Matsuzaki, M. Nakamata, H. Kayahara, and T. Nakagawa. 1996. Increased plasma level of platelet-activating factor (PAF) and decreased serum PAF acetylhydrolase (PAFAH) activity in adults with bronchial asthma. J. Investig. Allergol. Clin. Immunol. 6:22–29.

    PubMed  CAS  Google Scholar 

  41. Cuss, F. M., C. M. Dixon, and P. J. Barnes. 1986. Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man. Lancet 26:189–192.

    Article  Google Scholar 

  42. Chung, K. F., F. M. Cuss, and P. J. Barnes. 1989. Platelet activating factor: effects on bronchomotor tone and bronchial responsiveness in human beings. Allergy Proc. 10:333–337.

    Article  PubMed  CAS  Google Scholar 

  43. Louis, R. E., and M. F. Radermecker. 1996. Acute bronchial obstruction following inhalation of PAF in asthmatic and normal subjects: comparison with methacholine. Eur. Respir. J. 9:1414–1420.

    Article  PubMed  CAS  Google Scholar 

  44. Adamus, W. S., H. O. Heuer, C. J. Meade, and J. C. Schilling. 1990. Inhibitory effects of the new PAF acether antagonist WEB-2086 on pharmacologic changes induced by PAF inhalation in human beings. Clin. Pharmacol. Ther. 47:456–462.

    Article  PubMed  CAS  Google Scholar 

  45. Hsieh, K. H.. 1991. Effects of PAF antagonist, BN52021, on the PAF-, methacholine-, and allergen-induced bronchoconstriction in asthmatic children. Chest 99:877–882.

    Article  PubMed  CAS  Google Scholar 

  46. Schauer, U., B. Koch, U. Michl, R. Jager, and C. H. Rieger. 1992. Enhanced production of platelet activating factor by peripheral granulocytes from children with asthma. Allergy 47:143–149.

    Article  PubMed  CAS  Google Scholar 

  47. Lin, C. C., and C. Y. Lin. 1997. Bronchoconstriction and eosinophil recruitment in guinea pig lungs after platelet activating factor administration. J. Asthma 34:153–160.

    Article  PubMed  CAS  Google Scholar 

  48. Lellouch-Tubiana, A., J. Lefort, M. T. Simon, A. Pfister, and B. B. Vargaftig. 1988. Eosinophil recruitment into guinea pig lungs after PAF-acether and allergen administration. Modulation by prostacyclin, platelet depletion, and selective antagonists. Am. Rev. Respir. Dis. 137:948–954.

    PubMed  CAS  Google Scholar 

  49. Yamamoto, H., M. Nagata, K. Tabe, I. Kimura, H. Kiuchi, Y. Sakamoto, K. Yamamoto, and Y. Dohi. 1993. The evidence of platelet activation in bronchial asthma. J. Allergy Clin. Immunol. 91:79–87.

    Article  PubMed  CAS  Google Scholar 

  50. Steiger, J., M. A. Bray, and N. Subramanian. 1987. Platelet activating factor (PAF) is a potent stimulator of porcine tracheal fluid secretion in vitro. Eur. J. Pharmacol. 142:367–372.

    Article  PubMed  CAS  Google Scholar 

  51. Kirsch, C. M., J. J. Brokaw, D. M. Prow, and G. W. White. 1992. Mechanism of platelet activating factor-induced vascular leakage in the rat trachea. Exp. Lung Res. 18:447–459.

    Article  PubMed  CAS  Google Scholar 

  52. Evans, T. W., K. F. Chung, D. F. Rogers, and P. J. Barnes. 1987. Effect of platelet-activating factor on airway vascular permeability: possible mechanisms. J. Appl. Physiol. 63:479–484.

    PubMed  CAS  Google Scholar 

  53. Rodriguez-Roisin, R., M. A. Felez, K. F. Chung, J. A. Barbera, P. D. Wagner, A. Cobos, P. J. Barnes, and J. Roca. 1994. Platelet-activating factor causes ventilation–perfusion mismatch in humans. J. Clin. Invest. 93:188–194.

    Article  PubMed  CAS  Google Scholar 

  54. Diaz, O., J. A. Barbera, R. Marrades, K. F. Chung, J. Roca, and R. Rodriguez-Roisin. 1997. Inhibition of PAF-induced gas exchange defects by beta-adrenergic agonists in mild asthma is not due to bronchodilation. Am. J. Respir. Crit. Care Med. 156:17–22.

    PubMed  CAS  Google Scholar 

  55. Gomez, F. P., J. Roca, J. A. Barbera, K. F. Chung, V. I. Peinado, and R. Rodriguez-Roisin. 1998. Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF-induced gas exchange abnormalities in mild asthma. Eur. Respir. J. 11:835–839.

    Article  PubMed  CAS  Google Scholar 

  56. Spencer, D. A., S. E. Green, J. M. Evans, P. J. Piper, and J. F. Costello. 1990. Platelet activating factor does not cause a reproducible increase in bronchial responsiveness in normal man. Clin. Exp. Allergy 20:525–532.

    Article  PubMed  CAS  Google Scholar 

  57. Gebremichael, I., and P. Leuenberger. 1992. Platelet-activating factor does not induce bronchial hyperreactivity in nonasthmatic subjects. Respiration 59:193–196.

    Article  PubMed  CAS  Google Scholar 

  58. Roca, J., M. A. Felez, K. F. Chung, J. A. Barbera, M. Rotger, C. Santos, and R. Rodriguez-Roisin. 1995. Salbutamol inhibits pulmonary effects of platelet activating factor in man. Am J. Respir. Crit. Care Med. 151:1740–1744.

    PubMed  CAS  Google Scholar 

  59. Masclans, J. R., J. A. Barbera, W. MacNee, J. Pavia, C. Piera, F. Lomena, K. F. Chung, J. Roca, and R. Rodriguez-Roisin. 1996. Salbutamol reduces pulmonary neutrophil sequestration of platelet-activating factor in humans. Am. J. Respir. Crit. Care Med. 154(2 Pt 1):529–532.

    PubMed  CAS  Google Scholar 

  60. Herbert, J. M., M. C. Laplace, A. Bernat, V. Salel, and J. P. Maffrand. 1992. Effect of SR 27417 on oedema formation induced in rabbit skin by platelet-activating factor or antigen. Eur. J. Pharmacol. 216:175–181.

    Article  PubMed  CAS  Google Scholar 

  61. Pirotzky, E., C. P. Page, R. Roubin, A. Pfister, W. Paul, J. Bonnet, and J. Benveniste. 1984. PAF-acether-induced plasma exudation in rat skin is independent of platelets and neutrophils. Microcirc. Endothelium Lymphatics 1:107–122.

    PubMed  CAS  Google Scholar 

  62. Echazarreta, A. L., I. Rahman, V. Peinado, J. A. Barbera, J. Roca, W. MacNee, and R. Rodriguez-Roisin. 2005. Lack of systemic oxidative stress during PAF challenge in mild asthma. Respir. Med. 99:519–523.

    Article  PubMed  Google Scholar 

  63. Gomez, F. P., R. Iglesia, J. Roca, J. A. Barbera, K. F. Chung, and R. Rodriguez-Roisin. 1998. The effects of 5-lipoxygenase inhibition by zileuton on platelet-activating-factor-induced pulmonary abnormalities in mild asthma. Am J. Respir. Crit. Care Med. 157(5 Pt 1):1559–1564.

    PubMed  CAS  Google Scholar 

  64. Spencer, D. A., J. M. Evans, S. E. Green, P. J. Piper, and J. F. Costello. 1991. Participation of the cysteinyl leukotrienes in the acute bronchoconstriction response to inhaled platelet activating factor in man. Thorax 46:441–445.

    PubMed  CAS  Google Scholar 

  65. Kidney, J. C., S. M. Ridge, K. F. Chung, and P. J. Barnes. 1993. Inhibition of platelet-activating factor-induced bronchoconstriction by the leukotriene D4 receptor antagonist ICI 204,219. Am. Rev. Respir. Dis. 147:215–217.

    PubMed  CAS  Google Scholar 

  66. Chung, K. F., H. Aizawa, G. D. Leikauf, I. F. Ueki, T. W. Evans, and J. A. Nadel. 1986. Airway hyperresponsiveness induced by platelet-activating factor: role of thromboxane generation. J. Pharmacol. Exp. Ther. 236:580–584.

    PubMed  CAS  Google Scholar 

  67. Karasawa, K., A. Harada, N. Satoh, K. Inoue, and M. Setaka. 2003. Plasma platelet activating factor-acetylhydrolase (PAF-AH). Prog. Lipid Res. 42:93–114.

    Article  PubMed  CAS  Google Scholar 

  68. Stafforini, D. M., K. Satoh, D. L. Atkinson, L. W. Tjoelker, C. Eberhardt, H. Yoshida, T. Imaizumi, S. Takamatsu, G. A. Zimmerman, T. M. McIntyre, P. W. Gray, and S. M. Prescott. 1996. Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase. J. Clin. Invest. 97:2784–2791.

    Article  PubMed  CAS  Google Scholar 

  69. Ito, S., E. Noguchi, M. Shibasaki, K. Yamakawa-Kobayashi, H. Watanabe, and T. Arinami. 2002. Evidence for an association between plasma platelet-activating factor acetylhydrolase deficiency and increased risk of childhood atopic asthma. J. Hum. Genet. 47:99–101.

    Article  PubMed  CAS  Google Scholar 

  70. Miwa, M., T. Miyake, T. Yamanaka, J. Sugatani, Y. Suzuki, S. Sakata, Y. Araki, and M. Matsumoto. 1988. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children. J. Clin. Invest. 82:1983–1991.

    Article  PubMed  CAS  Google Scholar 

  71. Stafforini, D. M., T. Numao, A. Tsodikov, D. Vaitkus, T. Fukuda, N. Watanabe, N. Fueki, T. M. McIntyre, G. A. Zimmerman, S. Makino, and S. M. Prescott. 1999. Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma. J. Clin. Invest. 103:989–997.

    Article  PubMed  CAS  Google Scholar 

  72. Satoh, N., K. Asano, K. Naoki, K. Fukunaga, M. Iwata, M. Kanazawa, and K. Yamaguchi. 1999. Plasma platelet-activating factor acetylhydrolase deficiency in Japanese patients with asthma. Am. J. Respir. Crit. Care Med. 159:974–979.

    PubMed  CAS  Google Scholar 

  73. Triggiani, M., V. De Marino, M. Sofia, S. Faraone, G. Ambrosio, L. Carratu, and G. Marone. 1997. Characterization of platelet-activating factor acetylhydrolase in human bronchoalveolar lavage. Am. J. Respir. Crit. Care Med. 156:94–100.

    PubMed  CAS  Google Scholar 

  74. Naoki, K., K. Asano, N. Satoh, K. Fukunaga, T. Oguma, T. Shiomi, Y. Suzuki, T. Nakajima, K. Niimi, Y. Shiraishi, A. Ishizaka, and K. Yamaguchi. 2004. PAF responsiveness in Japanese subjects with plasma PAF acetylhydrolase deficiency. Biochem. Biophys. Res. Commun. 317:205–210.

    Article  PubMed  CAS  Google Scholar 

  75. Henig, N. R., M. L. Aitken, M. C. Liu, A. S. Yu, W. R. Henderson, Jr. 2000. Effect of recombinant human platelet-activating factor-acetylhydrolase on allergen-induced asthmatic responses. Am. J. Respir. Crit. Care Med. 162:523–527.

    PubMed  CAS  Google Scholar 

  76. Hozawa, S., Y. Haruta, S. Ishioka, and M. Yamakido. 1995. Effects of a PAF antagonist, Y-24180, on bronchial hyperresponsiveness in patients with asthma. Am. J. Respir. Crit. Care Med. 152:1198–1202.

    PubMed  CAS  Google Scholar 

  77. Kagoshima, M., N. Tomomatsu, Y. Iwahisa, S. Yamaguchi, M. Matsuura, Y. Kawakami, and M. Terasawa. 1997. Suppressive effects of Y-24180, a receptor antagonist to platelet activating factor (PAF), on antigen-induced asthmatic responses in guinea pigs. Inflamm. Res. 46:147–153.

    Article  PubMed  CAS  Google Scholar 

  78. Spence, D. P., S. L. Johnston, P. M. Calverley, P. Dhillon, C. Higgins, E. Ramhamadany, S. Turner, A. Winning, J. Winter, and S. T. Holgate. 1994. The effect of the orally active platelet-activating factor antagonist WEB 2086 in the treatment of asthma. Am. J. Respir. Crit. Care Med. 149:1142–1148.

    PubMed  CAS  Google Scholar 

  79. Kuitert, L. M., R. M. Angus, N. C. Barnes, P. J. Barnes, M. F. Bone, K. F. Chung, A. J. Fairfax, T. W. Higenbotham, B. J. O'Connor, B. Piotrowska, J. Rozniecki, S. Uden, E. Hayden, and C. J. Willard. 1995. Effect of a novel potent platelet-activating factor antagonist, modipafant, in clinical asthma. Am. J. Respir. Crit. Care Med. 151:1331–1335.

    PubMed  CAS  Google Scholar 

  80. Evans, D. J., P. J. Barnes, M. Cluzel, and B. J. O'Connor. 1997. Effects of a potent platelet-activating factor antagonist, SR27417A, on allergen-induced asthmatic responses. Am. J. Respir. Crit. Care Med. 156:11–16.

    PubMed  CAS  Google Scholar 

  81. Kuitert, L. M., K. P. Hui, S. Uthayarkumar, W. Burke, A. C. Newland, S. Uden, and N. C. Barnes. 1993. Effect of the platelet-activating factor antagonist UK-74,505 on the early and late response to allergen. Am. Rev. Respir. Dis. 147:82–86.

    PubMed  CAS  Google Scholar 

  82. Gomez, F. P., R. M. Marrades, R. Iglesia, J. Roca, J. A. Barbera, K. F. Chung, and R. M. Rodriguez-Roisin. 1999. Gas exchange response to a PAF receptor antagonist, SR 27417A, in acute asthma: a pilot study. Eur. Respir. J. 14:622–626.

    Article  PubMed  CAS  Google Scholar 

  83. Tjoelker, L. W., C. Wilder, C. Eberhardt, D. M. Stafforini, G. Dietsch, B. Schimpf, S. Hooper, H. Le-Trong, L. S. Cousens, G. A. Zimmerman, Y. Yamada, T. M. McIntyre, S. M. Prescott, and P. W. Gray. 1995. Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature 374:549–553.

    Article  PubMed  CAS  Google Scholar 

  84. Henderson, W. R. , J. Lu, K. M. Poole, G. N. Dietsch, and E. Y. Chi. 2000. Recombinant human platelet-activating factor-acetylhydrolase inhibits airway inflammation and hyperreactivity in mouse asthma model. J. Immunol. 164:3360–3367.

    PubMed  CAS  Google Scholar 

  85. Billah, M. M., R. W. Egan, A. K. Ganguly, M. J. Green, W. Kreutner, J. J. Piwinski, M. I. Siegel, F. J. Villani, and J. K. Wong. 1991. Discovery and preliminary pharmacology of Sch 37370, a dual antagonist of PAF and histamine. Lipids 26:1172–1174.

    Article  PubMed  CAS  Google Scholar 

  86. Billah, M. M., H. G. Gilchrest, S. P. Eckel, C. A. Granzow, P. J. Lawton, E. Radwanski, M. D. Brannan, M. B. Affrime, J. D. Christopher, and W. Richards. 1992. Differential plasma duration of antiplatelet-activating factor and antihistamine activities of oral Sch 37370 in humans. Clin. Pharmacol. Ther. 52:151–159.

    Article  PubMed  CAS  Google Scholar 

  87. Soyombo, O., B. W. Spur, and T. H. Lee. 1994. Effects of lipoxin A4 on chemotaxis and degranulation of human eosinophils stimulated by platelet-activating factor and N-formyl-l-methionyl-l-leucyl-l-phenylalanine. Allergy 49:230–234.

    Article  PubMed  CAS  Google Scholar 

  88. Filep, J. G., C. Zouki, N. A. Petasis, M. Hachicha, and C. N. Serhan. 1999. Anti-inflammatory actions of lipoxin A(4) stable analogs are demonstrable in human whole blood: modulation of leukocyte adhesion molecules and inhibition of neutrophil–endothelial interactions. Blood 94:4132–4142.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Chair and Clinical Department of Internal Diseases, Allergology and Clinical Immunology, Medical University of Silesia, Katowice, Poland

    A. Kasperska-Zajac, Z. Brzoza & B. Rogala

  2. Chair and Clinical Department of Internal Diseases, Allergology and Clinical Immunology, ul. 3-go Maja 13-15, 41-800, Zabrze, Poland

    A. Kasperska-Zajac

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  1. A. Kasperska-Zajac
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  2. Z. Brzoza
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  3. B. Rogala
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Correspondence to A. Kasperska-Zajac.

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Kasperska-Zajac, A., Brzoza, Z. & Rogala, B. Platelet Activating Factor as a Mediator and Therapeutic Approach in Bronchial Asthma. Inflammation 31, 112–120 (2008). https://doi.org/10.1007/s10753-007-9056-9

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  • DOI: https://doi.org/10.1007/s10753-007-9056-9

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