Journal Mobile Options
Table of Contents
Vol. 94, No. 2, 2008
Issue release date: August 2008
Neonatology 2008;94:79–86
(DOI:10.1159/000115949)

Maternal Betamethasone and Chorioamnionitis Induce Different Collagenases during Lung Maturation in Fetal Sheep

Sweet D.G. · Huggett M.T. · Warner J.A. · Moss T.J.M. · Kloosterboer N. · Halliday H.L. · Newnham J.P. · Kallapur S.G. · Jobe A.H. · Kramer B.W.
aDepartment of Child Health, The Queen’s University of Belfast, bSchool of Biological Sciences, University of Southampton, UK; cSchool of Women’s and Infants’ Health, University of Western Australia, Perth, W.A., Australia; dDivision of Pulmonary Biology, University of Cincinnati Medical Centre, Cincinnati, Ohio, USA; eDepartment of Pediatrics, University Hospital Maastricht, Maastricht, The Netherlands

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: Fetal lung maturation occurs after both maternal corticosteroid administration and chorioamnionitis. The effectors of this antenatally-induced lung maturation are not understood. Matrix metalloproteinases (MMPs) 2 and 9 are type-IV collagenases that can degrade alveolar basement membranes. Objectives: We hypothesized that the structural changes of lung maturation by both antenatal corticosteroid treatment and chorioamnionitis would be associated with increases in these MMPs. Methods: 64 pregnant ewes were randomly assigned to one of four treatment groups: intra-amniotic injection of 10 mg endotoxin, maternal intramuscular injection of 0.5 mg/kg betamethasone, both treatments combined or saline-treated controls. We quantified MMP-2 which is derived from connective tissue and MMP-9 which is predominantly derived from neutrophils in fetal lung fluid of lambs after maternal corticosteroid therapy and induction of chorioamnionitis and the combination of both therapies given at 109–111 days’ gestational age with delivery 1, 5 or 15 days later. Results: Betamethasone, endotoxin and the combined treatments increased both surfactant pool size, lung gas volume and reduced alveolar wall thickness at 15 days. MMP-2 concentration was increased after betamethasone. MMP-9 concentration increased after endotoxin-induced chorioamnionitis but decreased by the combined treatments. Conclusion: Lung maturation via different pathways may use different forms of collagenases for remodelling lung structure.



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. Ammari A, Suri M, Milisavljevic V, Sahni R, Bateman D, Sanocka U, Ruzal-Shapiro C, Wung JT, Polin RA: Variables associated with the early failure of nasal CPAP in very low birth weight infants. J Pediatr 2005;147:341–347.
  2. Halliday HL: Evidence-based neonatal care. Best Pract Res Clin Obstet Gynaecol 2005;19:155–166.
  3. Grier DG, Halliday HL: Effects of glucocorticoids on fetal and neonatal lung development. Treat Respir Med 2004;3:295–306.
  4. Roberts D, Dalziel S: Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006;3:CD004454.
  5. Ikegami M, Polk D, Jobe A: Minimum interval from fetal betamethasone treatment to postnatal lung responses in preterm lambs. Am J Obstet Gynecol 1996;174:1408–1413.
  6. Jobe AH, Newnham JP, Willet KE, Sly P, Ervin MG, Bachurski C, Possmayer F, Hallman M, Ikegami M: Effects of antenatal endotoxin and glucocorticoids on the lungs of preterm lambs. Am J Obstet Gynecol 2000;182:401–408.
  7. Kramer BW, Moss TJ, Willet KE, Newnham JP, Sly PD, Kallapur SG, Ikegami M, Jobe AH: Dose and time response after intraamniotic endotoxin in preterm lambs. Am J Respir Crit Care Med 2001;164:982–988.
  8. Kallapur SG, Willet KE, Jobe AH, Ikegami M, Bachurski CJ: Intra-amniotic endotoxin: chorioamnionitis precedes lung maturation in preterm lambs. Am J Physiol 2001;280:L527–L536.
  9. Kallapur SG, Bachurski CJ, Le Cras TD, Joshi SN, Ikegami M, Jobe AH: Vascular changes after intra-amniotic endotoxin in preterm lamb lungs. Am J Physiol 2004;287:L1178–L1185.
  10. Willet KE, Jobe AH, Ikegami M, Newnham J, Brennan S, Sly PD: Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs. Pediatr Res 2000;48:782–788.
  11. Kramer BW, Kramer S, Ikegami M, Jobe AH: Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol 2002;283:L452–L459.
  12. Moss TJ, Newnham JP, Willett KE, Kramer BW, Jobe AH, Ikegami M: Early gestational intra-amniotic endotoxin: lung function, surfactant, and morphometry. Am J Respir Crit Care Med 2002;165:805–811.
  13. Lemaitre V, D’Armiento J: Matrix metalloproteinases in development and disease. Birth Defects Res C Embryo Today 2006;78:1–10.
  14. Dik WA, van Kaam AH, Dekker T, Naber BA, Janssen DJ, Kroon AA, Zimmermann LJ, Versnel MA, Lutter R: Early increased levels of matrix metalloproteinase-9 in neonates recovering from respiratory distress syndrome. Biol Neonate 2006;89:6–14.
  15. Gueders MM, Foidart JM, Noel A, Cataldo DD: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: potential implications in asthma and other lung diseases. Eur J Pharmacol 2006;533:133–144.
  16. Sweet DG, Curley AE, Chesshyre E, Pizzotti J, Wilbourn MS, Halliday HL, Warner JA: The role of matrix metalloproteinases-9 and -2 in development of neonatal chronic lung disease. Acta Paediatr 2004;93:791–796.
  17. Curley AE, Sweet DG, Thornton CM, O’Hara MD, Chesshyre E, Pizzotti J, Wilbourn MS, Halliday HL, Warner JA: Chorioamnionitis and increased neonatal lung lavage fluid matrix metalloproteinase-9 levels: implications for antenatal origins of chronic lung disease. Am J Obstet Gynecol 2003;188:871–875.
  18. Kallapur SG, Kramer BW, Moss TJ, Newnham JP, Jobe AH, Ikegami M, Bachurski CJ: Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs. Am J Physiol 2003;284:L633–L642.
  19. Kramer BW, Ikegami M, Moss TJ, Nitsos I, Newnham JP, Jobe AH: Antenatal betamethasone changes cord blood monocyte responses to endotoxin in preterm lambs. Pediatr Res 2004;55:764–768.
  20. Newnham JP, Moss TJ, Padbury JF, Willet KE, Ikegami M, Ervin MG, Sly P, Jobe A: The interactive effects of endotoxin with prenatal glucocorticoids on short-term lung function in sheep. Am J Obstet Gynecol 2001;185:190–197.
  21. Newnham JP, Kallapur SG, Kramer BW, Moss TJ, Nitsos I, Ikegami M, Jobe AH: Betamethasone effects on chorioamnionitis induced by intra-amniotic endotoxin in sheep. Am J Obstet Gynecol 2003;189:1458–1466.
  22. Ikegami M, Jobe AH, Newnham J, Polk DH, Willet KE, Sly P: Repetitive prenatal glucocorticoids improve lung function and decrease growth in preterm lambs. Am J Respir Crit Care Med 1997;156:178–184.
  23. Jobe AH, Newnham JP, Willet KE, Moss TJ, Gore Ervin M, Padbury JF, Sly P, Ikegami M: Endotoxin-induced lung maturation in preterm lambs is not mediated by cortisol. Am J Respir Crit Care Med 2000;162:1656–1661.
  24. Kleiner DE, Stetler-Stevenson WG: Quantitative zymography: detection of picogram quantities of gelatinases. Anal Biochem 1994;218:325–329.
  25. Burri PH: Structural aspects of postnatal lung development – alveolar formation and growth. Biol Neonate 2006;89:313–322.
  26. Massaro D, Massaro GD: Dexamethasone accelerates postnatal alveolar wall thinning and alters wall composition. Am J Physiol 1986;251:R218–R224.
  27. Bry K, Lappalainen U: Pathogenesis of bronchopulmonary dysplasia: the role of interleuken-1β in the regulation of inflammation-mediated pulmonary retinoic Acid pathways in transgenic mice. Semin Perinatol 2006;30:121–128.
  28. Atkinson JJ, Holmbeck K, Yamada S, Birkedal-Hansen H, Parks WC, Senior RM: Membrane-type 1 matrix metalloproteinase is required for normal alveolar development. Dev Dyn 2005;232:1079–1090.
  29. Cataldo DD, Tournoy KG, Vermaelen K, Munaut C, Foidart JM, Louis R, Noel A, Pauwels RA: Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen- induced airway inflammation. Am J Pathol 2002;161:491–498.
  30. Corbel M, Caulet-Maugendre S, Germain N, Molet S, Lagente V, Boichot E: Inhibition of bleomycin-induced pulmonary fibrosis in mice by the matrix metalloproteinase inhibitor batimastat. J Pathol 2001;193:538–545.
  31. Cederqvist K, Sorsa T, Tervahartiala T, Maisi P, Reunanen K, Lassus P, Andersson S: Matrix metalloproteinases-2, -8, and -9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress. Pediatrics 2001;108:686–692.
  32. Watterberg KL, Demers LM, Scott SM, Murphy S: Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996;97:210–215.
  33. Kent A, Dahlstrom JE: Chorioamnionitis/funisitis and the development of bronchopulmonary dysplasia. J Paediatr Child Health 2004;40:356–359.
  34. Speer CP: New insights into the pathogenesis of pulmonary inflammation in preterm infants. Biol Neonate 2001;79:205–209.
  35. Bland RD: Neonatal chronic lung disease in the post-surfactant era. Biol Neonate 2005;88:181–191.
  36. Cao L, Liu C, Cai B, Jia X, Kang L, Speer CP, Sun B: Nuclear factor-κB expression in alveolar macrophages of mechanically ventilated neonates with respiratory distress syndrome. Biol Neonate 2004;86:116–123.
  37. Sosenko IR, Jobe AH: Intraamniotic endotoxin increases lung antioxidant enzyme activity in preterm lambs. Pediatr Res 2003;53:679–683.


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