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In vivo responses of mouse blood cells to platelet-activating factor (PAF): Role of the mediators of anaphylaxis

  • Allergy and Histamine
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Abstract

Intravenous injection of platelet-activating factor (PAF) (0.36 μmol/kg b.w.) in mice induced severe hemoconcentration, leucopenia, thrombocytopenia and finally the death of 85% of the tested animals. Combined inhibition of histamine and serotonin by promethazine and chlorpromazine, 6.24 and 3.12 mg/kg b.w. subcutaneously, protected the mice from PAF in part, reducing the death rate to 43%. These drugs did not protect the mice against the PAF-induced hemoconcentration, leucopenia and thrombocytopenia. Sulfinpyrazone (100 mg/kg b.w.) intravenously was the most effective both in protecting mice from PAF-induced death, reducing the death rate to 17%, and from thrombocytopenia, although hemoconcentration persisted. These results indicated that an important component of the PAF-induced systemic effects is mediated by reactions which can be inhibited by sulfinpyrazone. Furthermore, PAF-induced thrombocytopenia is not a direct PAF effect since it can be inhibited by sulfinpyrazone.

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References

  1. J. M. Young, P. J. Maloney, S. N. Jubb and J. S. Clark,Pharmacological investigation of the mechanisms of platelet-activating factor induced mortality in the mouse. Prostaglandins30, 545–551 (1985).

    Article  PubMed  Google Scholar 

  2. T. Yamada, K. Tomioka, M. Saito, M. Horie, T. Mase, H. Hara and H. Nagaoka,Pharmacological properties of YM264, a potent and orally active antagonist of platelet-activating factor. Arch. Int. Pharmacodyn. Ther.308, 123–136 (1990).

    PubMed  Google Scholar 

  3. H. Tsunoda, Y. Sakuma, K. Harada, K. Muramoto, S. Katayama, T. Horie, N. Shimomura, R. Clark, S. Miyazawa, K. Okano, Y. Machida, K. Katayama and I. Yamatsu,Pharmacological activities of novel thienodiazepine derivative as a platelet-activating factor antagonist. Arzneim.-forsch./Drug Res.40, 1201–1205 (1990).

    Google Scholar 

  4. J. M. Herbet, A. Bernat, G. Valette, V. Gigo, A. Lale, M. C. Laplace, L. Lespy, P. Savi, J. P. Maffrand and G. Le Fur,Biochemical and pharmacological activities of SR27417, a highly potent, long-acting platelet-activating factor receptor antagonist. J. Pharmacol. Exp. Ther.259, 44–51 (1991).

    PubMed  Google Scholar 

  5. D. E. Guinn, J. B. Summers, H. R. Heyman, R. G. Conway, D. A. Rhein, D. H. Albert, T. Magoc and G. W. Carter,Synthesis and structure-activity relationships of a series of novel benzopyran-containing platelet-activating factor antagonists. J. Med. Chem.35, 2055–2061 (1992).

    Article  PubMed  Google Scholar 

  6. E. Lanara, C. Vakirtzi-Lemonias, L. G. Kritikou and C. A. Demopoulos,Response of mice and mouse platelets to acetyl glyceryl ether phosphorylcholine. Biochem. Biophys. Res. Commun.109, 1148–1156 (1982).

    PubMed  Google Scholar 

  7. D. Kelefiotis, E. Lanara, C. Vakirtzi-Lemonias, A. Siafaca, M. Mavris, M. Lazanas and C. A. Demopoulos,Study of digoxin as inhibitor of the in vivo effects of acetyl glyceryl ether phosphorylcholine (AGEPC) in mice. Life Sci.42, 623–633 (1987).

    Article  Google Scholar 

  8. D. H. Namm, A. S. Taderalli and J. A. High,Species specificity of the platelet responses to 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine. Thromb. Res.25, 341–350 (1982).

    Article  PubMed  Google Scholar 

  9. Z.-I. Terashita, Y. Imura and K. Nishikawa,Inhibition by CV-3988 of the binding of [3H]-platelet activating factor (PAF) to the platelet. Biochem. Pharmacol.34, 1491–1495 (1985).

    Article  PubMed  Google Scholar 

  10. B. B. Vargaftig, M. Chignard, J. Benveniste, J. Lefort and F. Wal,Background and present status of research on platelet-activating factor (PAF-acether). Ann. N.Y. Acad. Sci.370, 119–137 (1981).

    PubMed  Google Scholar 

  11. P. Inarrea, J. Gomez-Cambronero, M. Nieto and M. Sancez Crespo,Characteristics of the binding of platelet-activating factor to platelets of different animal species. Eur. J. Pharmacol.105, 309–315 (1984).

    Article  PubMed  Google Scholar 

  12. E. T. Iff and N. M. Vaz,Mechanisms of anaphylaxis in the mouse: Similarity of shock induced by anaphylaxis and by mixtures of histamine and serotonin. Int. Arch. Allergy30, 313–322 (1966).

    PubMed  Google Scholar 

  13. B. N. Halpern, T. Neveu and S. Spector,On the nature of the chemical mediators involved in anaphlyactic reactions in mice. Br. J. Pharmacol.20, 389–398 (1963).

    Google Scholar 

  14. M. Chignard, F. Wal, J. Lefort and B. B. Vargaftig,Inhibition by sulphinpyrazone of the platelet-dependent bronchoconstriction due to platelet-activating factor (PAF-acether) in the guinea-pig. Eur. J. Pharmacol.78, 71–79 (1982).

    Article  PubMed  Google Scholar 

  15. C. A. Demopoulos, R. N. Pinckard and D. J. Hanahan,Platelte-activating factor. Evidence for 1-O-alkyl-2-acetylsn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators). J. Biol. Chem.254, 9355–9358 (1979).

    PubMed  Google Scholar 

  16. L. M. McManus, R. N. Pinckard, F. A. Fitzpatrick, R. A. O'Rourke, M. H. Crawford and D. J. Hanahan,Acetyl glyceryl ether phosphorylcholine: Intravascular alterations following intravenous infusion into the baboon. Lab. Invest.45, 303–307 (1981).

    PubMed  Google Scholar 

  17. L. M. McManus, D. J. Hanahan, C. A. Demopoulos and R. N. Pinckard,Pathobiology of the intravenous infusion of acetyl glyceryl ether phosphorylcholine (AGEPC), a synthetic platelet-activating factor (PAF), in the rabbit. J. Immunol.124, 2919–2924 (1980).

    PubMed  Google Scholar 

  18. C. A. Demopoulos, G. E. Tsabikakis and V. M. Kapoulas,Intravascular pathobiology of acetyl glyceryl ether phosphorylcholine (AGEPC), a synthetic platelet-activating factor (PAF). I. Intravenous infusion in guinea pigs. Immunol. Lett.3, 133–135 (1981).

    PubMed  Google Scholar 

  19. D. Kelefiotis and C. Vakirtzi-Lemonias,Effect of non-steroidal anti-inflammatory drugs on alkyl-acetyl-glycerol-phosphocholine-induced anaphylactic shock in mice. Biochem. Soc. Trans.14, 94–95 (1986).

    Google Scholar 

  20. A. Myers, E. Ramey and P. Ramwell,Glucocorticoid protection against PAF-acether toxicity in mice. Br. J. Pharmacol.79, 595–598 (1983).

    PubMed  Google Scholar 

  21. L. Levesque, R. C. Gaureault and F. Marceau,The interaction of 3,5-pyrazolidinedione drugs with receptors for f-Met-Leu-Phe on human neutrophil leucocytes: A study of structure-activity relationship. Can. J. Physiol. Pharmacol.69, 419–425 (1991).

    PubMed  Google Scholar 

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Kelefiotis, D., Vakirtzi-Lemonias, C. In vivo responses of mouse blood cells to platelet-activating factor (PAF): Role of the mediators of anaphylaxis. Agents and Actions 40, 150–156 (1993). https://doi.org/10.1007/BF01984054

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