Skip to main content
Log in

Effect of ketotifen on the distribution and degranulation of uterine eosinophils in estrogen-treated rats

  • Allery, Histamine and Kinins
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

Eosinophil leukocytes migrate from the blood to the uterus under estrogen stimulation, redistribute through uterine extravascular compartment, degranulate in the organ, and release agents that are involved in several parameters of estrogen action. Agents that induce blood eosinopenia, block their migration to the uterus, interfere with their redistribution within the organ or modify their degranulation, selectively interfere with eosinophil-mediated responses to estrogen. The present study investigated whether ketotifen, an antiallergic agent that inhibits allergen-induced eosinophil degranulation, interferes with estrogen-induced eosinophil migration to the uterus and their subsequent degranulation. Ketotifen does not interfere with estrogen-induced eosinophil accumulation in the uterus, but decreases the proportion of eosinophils located in endometrium and inhibitis their degranulation. These results suggest that neither histamine, calcium or slow reacting substance of anaphilaxis are involved in eosinophil migration to the uterus. The inhibition by ketotifen of eosinophil degranulation may diminish eosinophil migration through extravascular compartment via a decrease in the release from degranulating eosinophils of enzymes required for this migration. It is possible that the inhibition by ketotifen of both, eosinophil degranulation and eosinophil motility through uterine extravascular compartment, interfere with eosinophil-mediated responses to estrogen or with other functions of these cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. T. Rytomäa,Organ distribution and histochemical properties of eosinophil granulocytes in rat. Acta Pathol. Microbiol. Scand.50, Suppl.140, 1–118 (1960).

    Google Scholar 

  2. E. G. Bassett,Infiltration of eosinophils into the modified connective tissue of oestrus and pregnant animals. Nature194, 1259–1261 (1962).

    Google Scholar 

  3. A. Tchernitchin, J. Roorijck, X. Tchernitchin, J. Vandenhende and P. Galand,Dramatic early increse in uterine eosinophils after oestrogen administration. Nature248, 142–143 (1974).

    PubMed  Google Scholar 

  4. A. Tchernitchin, X. Tchernitchin and P. Galand,Correlation of estrogen-induced uterine eosinophilia with other parameters of estrogen stimulation, produced with estradiol-17β and estriol. Experientia31, 993–994 (1975).

    PubMed  Google Scholar 

  5. G. Grunert, M. Porcia and A. N. Tchernitchin,Differential potency of oestradiol-17β and diethylstilboestrol on separate groups of responses in the rat uterus. J. Endocrinol.110, 103–114 (1986).

    PubMed  Google Scholar 

  6. A. Tchernitchin,Fine structure of rat uterine eosinophils and the possible role of eosinophils in the mechanism of estrogen action. J. Steroid Biochem.4, 277–282 (1973).

    PubMed  Google Scholar 

  7. A. Tchernitchin,The role of eosinophil receptors in the non-genomic response to oestrogens in the uterus. J. Steroid Biochem.11, 417–424 (1979).

    PubMed  Google Scholar 

  8. A. N. Tchernitchin, M. A. Mena, A. Rodriguez and M. Maturana,Radioautographic localization of estrogen receptors in the rat uterus: a tool for the study of classical and nontraditional mechanisms of hormone action. In:Localization of Putative Steroid Receptors, vol. 1, (Eds. L. P. Pertschuk and S. H. Lee) pp. 5–37, CRC Press, Boca Raton, Florida 1985.

    Google Scholar 

  9. A. N. Tchernitchin and P. Galand,Dissociation of separate mechanisms of estrogen action by actinomycin D. Experientia38, 511–513 (1982).

    PubMed  Google Scholar 

  10. A. N. Tchernitchin,Eosinophil-mediated non-genomic parameters of estrogen stimulation: A separate group of responses mediated by an independent mechanism. J. Steroid Biochem.19, 95–100 (1983).

    PubMed  Google Scholar 

  11. A. Tchernitchin, J. Rooryck, X. Tchernitchin, J. Vandenhende and P. Galand,Effects of cortisol on uterine eosinophilia and other oestrogenic responses. Mol. Cell. Endocrinol.2, 331–337 (1975).

    PubMed  Google Scholar 

  12. N. Soto and A. Tchernitchin,Colchicine-estrogen interactions. Experientia35, 558–559 (1979).

    PubMed  Google Scholar 

  13. G. Grunert and A. N. Tchernitchin,Effect of progesterone on the non-genomic response to oestrogen in the rat. J. Endocrinol.94, 307–315 (1982).

    PubMed  Google Scholar 

  14. G. Grunert, M. Porcia, G. Neumann, S. Sepúlveda and A. N. Tchernitchin,Progesterone interaction with eosinophils and with responses already induced by oestrogen in the uterus. J. Endocrinol.102, 295–303 (1984).

    PubMed  Google Scholar 

  15. W. K. Podleski, B. A. Panaszek, J. L. Schmidt and R. B. Burns,Inhibition of eosinophils degranulation by ketotifen in a patient with milk allergy, manifested as bronchial asthma—an electron microscopic study. Agents and Actions15, 177–181 (1984).

    PubMed  Google Scholar 

  16. A. N. Tchernitchin and P. Galand,Oestrogen levels in the blood, not in the uterus, determine uterine eosinophilia and oedema. J. Endocrinol.99, 123–130 (1983).

    PubMed  Google Scholar 

  17. G. Grunert, G. Neumann, M. Porcia and A. N. Tchernitchin,The estrogenic responses to clomiphene in the different cell-types of the rat uterus: Morphometrical evaluation. Biol. Reprod.37, 527–538 (1987).

    PubMed  Google Scholar 

  18. A. N. Tchernitchin, J. Barrera, P. Arroyo, M. A. Mena, K. Vilches and G. Grunert,Degranulatory action of estratiol on blood eosinophil leukocytes in vivo and in vitro. Agents and Actions17, 60–66 (1985).

    PubMed  Google Scholar 

  19. A. Kumagal and H. Tomioka,Pharmacological models for characterizing new anti-asthmatics. Triangle17, 135–140 (1978).

    PubMed  Google Scholar 

  20. C. Greenwood,The pharmacology of ketotifen. Chest82 Suppl., 45S-48S (1982).

    PubMed  Google Scholar 

  21. B. Josefsson,Studies on eosinophil granulocytes. V. Evidence against the role of histamine as a mediator of eosinophilia in the uterus of the rat. Acta Endocrinol.58, 532–536 (1968).

    PubMed  Google Scholar 

  22. K. E. Clark, D. B. Farley, D. E. van Orden and M. J. Brody,Estrogen-induced uterine hyperemia and edema persist during histamine receptor blockade. Proc. Soc. Exp. Biol. Med.156, 411–416 (1977).

    PubMed  Google Scholar 

  23. N. Terada, T. Yamane, K. Matsumoto, H. Asai and Y. Kitamura,Estrogen-induced increase in eosinophil number and peroxidase activity in uterus of genetically mast cell-deficient W/Wv mice. Biol. Reprod.33, 899–901 (1985).

    PubMed  Google Scholar 

  24. D. A. Lowe and B. P. Richardson,The effects of cyproheptadine, ketotifen and sodium nitroprusside on mechanical activity and calcium uptake in guinea-pig Taenia coli in vitro. Prog. Resp. Res.14, 134–140 (1980).

    Google Scholar 

  25. M. A. Mena, G. Grunert, M. S. Mansilla, M. E. Lúcia, M. I. Pizarro, P. A. Hidalgo and A. N. Tchernitchin,Inhibition of non-genomic responses to oestrogen in the rat uterus by testosterone propionate. J. Reprod. Fertil.74, 1–7 (1985).

    PubMed  Google Scholar 

  26. N. Sabag, M. A. Castrillón and A. Techernitchin,Cortisol-induced migration of eosinophil leukocytes to lymphoid organs. Experientia34, 666–667 (1978).

    PubMed  Google Scholar 

  27. A. N. Tchernitchin, M. A. Castrillón and A. Rodriguez,Cellular distribution of dexamethasone in rabbit spleen and lymph nodes. Agents and Actions15, 588–593 (1984).

    PubMed  Google Scholar 

  28. A. N. Tchernitchin, M. A. Mena, J. Soto and C. Unda,The role of eosinophils in the action of estrogens and other hormones. Med. Sci. Res.17, 5–10 (1989).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Soto, J., Tchernitchin, A.N., Poloni, P. et al. Effect of ketotifen on the distribution and degranulation of uterine eosinophils in estrogen-treated rats. Agents and Actions 28, 198–203 (1989). https://doi.org/10.1007/BF01967401

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01967401

Keywords

Navigation