Journal Mobile Options
Table of Contents
Vol. 147, No. 2, 2008
Issue release date: September 2008
Int Arch Allergy Immunol 2008;147:140–146
(DOI:10.1159/000135701)

IgE-Independent Mast Cell Activation Augments Contractility of Nonpregnant and Pregnant Guinea Pig Myometrium

Bytautiene E. · Vedernikov Y.P. · Saade G.R. · Romero R. · Garfield R.E.
aDepartment of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Tex., and bPerinatology Research Branch, National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, Md., and Detroit, Mich., USA

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Background: We have previously shown that in sensitized guinea pigs premature labor can be induced by a type I hypersensitivity reaction. We further hypothesize that premature labor occurs due to increased uterine contractility caused by activation of mast cells and possibly eosinophils, and collective release of their mediators. The objective of this study was to test the hypothesis that IgE-independent mast cell degranulation could increase uterine contractility. Methods: Longitudinal uterine strips from nonpregnant and pregnant guinea pigs were incubated in organ chambers with vehicle, histamine H1, serotonin 5-HT2/5-HT1C, thromboxane A2, leukotriene D4 receptor antagonists, mast cell stabilizer, and cyclooxygenase or lipoxygenase inhibitors. Then, supernatant, obtained after activation of a mast cell line (MC/9) with compound 48/80, culture medium, or compound 48/80 alone were added. Cumulative concentration-response curves to histamine and serotonin were also obtained. Results: The supernatant and compound 48/80 significantly increased contractility of uterine strips. A mast cell stabilizer considerably reduced the effect of compound 48/80. Other substances attenuated uterine contractile responses to supernatant and compound 48/80, and responses varied depending on the pregnancy period. Histamine and serotonin increased contractility of uterine strips, and uterine sensitivity to these agents were dependent on gestational age. Conclusions: In summary, mast cells increase uterine contractility through multiple mediators, and uterine responses to these mediators are dependent on gestational age. We postulate that the simultaneous release of these mast cell/eosinophil mediators in the uterus could be a stimulus to trigger and/or maintain myometrial contractions during preterm and term labor.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Bytautiene E, Romero R, Vedernikov Y, Saade G, Garfield RE: Induction of premature labor and delivery by allergic reaction and prevention by histamine H1 receptor antagonist. Am J Obstet Gynecol 2004;191:1356–1361.
  2. Drudy L, Sheppard B, Bonnar J: Mast cells in the normal uterus and in dysfunctional uterine bleeding. Eur J Obstet Gynecol Reprod Biol 1991;39:193–201.
  3. Mori A, Zhai YL, Toki T, Nikaido T, Fujii S: Distribution and heterogeneity of mast cells in the human uterus. Hum Reprod 1997;12:368–372.
  4. Massey WA, Guo CB, Dvorak AM, Hubbard WC, Bhagavan BS, Cohan VL, et al: Human uterine mast cells. Isolation, purification, characterization, ultrastructure, and pharmacology. J Immunol 1991;5:1621–1627.
  5. Cruz MA, Gonzalez C, Acevedo CG, Sepulveda WH, Rudoph MI: Effects of histamine and serotonin on the contractility of isolated pregnant and nonpregnant human myometrium. Gynecol Obstet Invest 1989;28:1–4.
  6. Castelli MC, Vadora E, Bacchi MA, Molina E: In vitro effects of histamine on human pregnant myometrium contractility. Boll Soc Ital Biol Sper 1993;69:783–789.
  7. Bytautiene E, Vedernikov YP, Saade GR, Romero R, Garfield RE: Effect of histamine on phasic and tonic contractions of isolated uterine tissue from pregnant women. Am J Obstet Gynecol 2003;188:774–778.
  8. Rudolph MI, Reinicke K, Cruz MA, Gallardo V, Gonzalez C, Bardisa L: Distribution of mast cells and the effect of their mediators on contractility in human myometrium. Br J Obstet Gynecol 1993;100:1125–1130.
  9. Senchyna M, Crankshaw DJ: Characterization of the prostanoid TP receptor population in human nonpregnant myometrium. J Pharmacol Exp Ther 1996;279:262–270.
  10. Bennett PR, Elder MG, Myatt L: The effects of lipoxygenase metabolites of arachidonic acid on human myometrial contractility. Prostaglandins 1987;33:837–844.
  11. Abbas F, Amin Z, Burk RM, Krauss AH, Marshall K, Senior J, et al: A comparative study of thromboxane (TP) receptor mimetics and antagonists on isolated human umbilical artery and myometrium. Adv Exp Med Biol 1997;407:219–230.
  12. Goyal RK, Verma SC: Pharmacological investigations into the effects of histamine and histamine analogs on guinea pig and rat uterus. Agents Actions 1981;11:312–317.
  13. Bytautiene E, Vedernikov YP, Saade GR, Romero R, Garfield RE: Endogenous mast cell degranulation modulates cervical contractility in the guinea pig. Am J Obstet Gynecol 2002;186:438–445.
  14. Rudolph M, Bardisa L, Cruz MA, Reinicke K: Mast cells mediators evoke contractility and potentiate each other in mouse uterine horns. Gen Pharmacol 1992;23:833–836.
  15. Tabb TN: Immune control of myometrial contractility: role of mast cells; in Garfield RE, Tabb TN (eds): Control of Uterine Contractility. Boca Raton, CRC Press, 1994, pp 355–373.
  16. Weichman BM, Tucker SS: Contraction of guinea pig uterus by synthetic leukotrienes. Prostaglandins 1982;24:245–253.
  17. Lopez BA, Canete SR, Turnbull AC: Are leukotrienes involved in human uterine contractility? Br J Obstet Gynaecol 1989;96:568–573.

    External Resources

  18. Bytautiene E, Vedernikov YP, Saade G, Romero R, Garfield RE: Degranulation of uterine mast cell modifies contractility of isolated myometrium from pregnant women. Am J Obstet Gynecol 2004;191:1705–1710.
  19. Cantor H, Nabel G: Assay methods and systems utilizing mast cell clones. USA patent 4,559,310. 1985.
  20. Galli SJ, Dvorak AM, Marcum JA, Ishizaka T, Nabel G, Der SH, et al: Mast cell clones: a model for the analysis of cellular maturation. J Cell Biol 1982;95:435–444.
  21. Nahm DH, Tkaczyk C, Fukuishi N, Colucci-Guyon E, Gilfillan AM, Metcalfe DD: Identification of Fyn-binding proteins in MC/9 mast cells using mass spectrometry. Biochem Biophys Res Commun 2003;310:202–208.
  22. McCurdy JD, Lin TJ, Marshall JS: Toll-like receptor 4-mediated activation of murine mast cells. J Leukoc Biol 2001;70:977–984.
  23. Coleman HA, Hart JDE, Tonta MA, Parkington HC: Changes in the mechanisms involved in uterine contractions during pregnancy in guinea-pigs. J Physiol (Lond) 2000;523:785–798.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50