Skip to main content
Log in

Antioxidant Superoxide Dismutase Attenuates Increased Endothelial Permeability Induced By Platelet-Activating Factor

  • Original Article
  • Published:
The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

TO study the protective effects of the antioxidant superoxide dismutase (SOD) against platelet-activating factor (PAF)-induced endothelial permeability.

Methods

Endothelial cells (ECs) were isolated from human umbilical veins from normal pregnancies. The first passage (PI) ECs were grown in polycarbonate transwell filters. Confluent ECs were incubated with PAF at concentrations of 2, 5, and 10 [Lg/mLfor 2 hours or pretreated with superoxide dismutase. Endothelial monolayer permeability was then measured by EC electrical resistance or by the leakage of horseradish peroxide (HRP) passing through filters. Endothelial junctional protein distribution and expression of VE-cadherin and occludin were determined by fluorescent staining of endothelial monolayer and by Western blot analysis. mRNA expressions for VE-cadherin and occludin were determined by reverse transcriptase—polymerase chain reaction. Data are expressed as Ω · cm2 for electrical resistance and δ OD 470 nmfor HRP assay and presented as mean ± standard error of the mean. Analysis of variance was used for statistical analysis. A P value less than.05 was considered statistically significant.

Results

Endothelial cell electrical resistance was decreased and HRP leakage was increased in ECs treated with PAF. Intercellular gaps were formed at cell contact regions in ECs treated with PAF, as evaluated by staining of junctional protein VE-cadherin and occludin. The functional changes of the EC barrier and the formation of intercellular gaps induced by PAF were concentration dependent, which could be partially attenuated by pretreatment of ECs with SOD. Total cellular junctional protein expression and mRNA expression of VE-cadherin and occludin were not affected by PAF.

Conclusions

Increased EC monolayer permeability induced by platelet-activating factor is associated with disorganization of EC junctional protein distribution of VE-cadherin and occludin. Superoxide dismutase partially attenuated the PAF-induced increased endothelial monolayer permeability, which suggests that oxidative stress might be involved in the process of PAF-induced disturbances of endothelial barrier function, (f Soc Gynecol Investig 2003;10:5–10)

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. Rowland BL, Vermillion ST, Roundebush WE. Elevated circulating concentrations of platelet activating factor in preeclampsia. Am J Obstet Gynecol 2000;183:930–2.

    Article  CAS  Google Scholar 

  2. Maki N, Magness RR, Miyaura S, Gant NF, Johnston JM. Platelet-activating factor-acetylhydrolase activity in normotensive and hypertensive pregnancies. Am J Obstet Gynecol 1993;168:50–4.

    Article  CAS  Google Scholar 

  3. Ohshige A, Yoshimura T, Matsui K, Koyama H, Ito M, Oka-mura H. Reduced platelet-activating factor-acetylhydrolase activity in maternal plasma obtained from normotensive pregnant women destined to develop pregnancy-induced hypertension. Hypertens Pregn 1998;17:297–306.

    Article  Google Scholar 

  4. Bussolino F, Camussi G, Aglietta M, et al. Human endothelial cells are target for platelet-activating factor. I. Platelet-activating factor induces changes in cytoskeleton structures. J Immunol 1987;139:2439–46.

    CAS  PubMed  Google Scholar 

  5. Okayama N, Kevil CG, Correia L, et al. Nitric oxide enhances hydrogen peroxide-mediated endothelial permeability in vitro. Am J Physiol 1997;273:0581–7.

    Article  Google Scholar 

  6. Kevil CG, Oshima T, Alexander B, Coe LL, Alexander JS. H2O2-mediated permeability: Role of MAPK and occludin. Am J Physiol Cell Physiol 2000;279:C21–C30.

    Article  CAS  Google Scholar 

  7. Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 1973;52:2745–56.

    Article  CAS  Google Scholar 

  8. Wang Y, Adair CD, Coe L, Weeks JW, Lewis DF, Alexander JS. Activation of endothelial cells in preeclampsia: Increased neutrophilendothelial adhesion correlates with up-regulation of adhesion molecule P-selectin in human umbilical vein endothelial cells isolated from preeclampsia. J Soc Gynecol Invest 1998;5:237–43.

    CAS  Google Scholar 

  9. de Montellano PRO, David SK, Ator MA, Tew D. Mechanismbased inactivation of horseradish peroxidase by sodium azide. Formation of meco-Axidoprotoporphyrin IX. Biochemistry 1988;27:5470–6.

    Google Scholar 

  10. Lampugnani MG, Resnati M, Raiteri M, et al. A novel endothelial-specific membrane protein is a marker of cell-cell contacts. J Cell Biol 1992;118:1511–22.

    Article  CAS  Google Scholar 

  11. Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S. Occludin: A novel integral membrane protein localizing at tight junctions. J Cell Biol 1993;123:1777–88.

    Article  CAS  Google Scholar 

  12. Kevil CG, Okayama N, Trocha SD, et al. Expression of zonula occludins and adherens juntional proteins in human venous and arterial endothelial cells: Role of occludin in endothelial solute barriers. Microcirculation 1998;5:197–210.

    Article  CAS  Google Scholar 

  13. Ando-Akatsuka Y, Saitou M, Hirase T, et al. Interspecies diversity of the occludin sequence: cDNA cloning of human, mouse, dog, and rat-kangaroo homologues. J Cell Biol 1996;133:43–7.

    Article  CAS  Google Scholar 

  14. Wang Y, Gu Y, Granger DN, Roberts JM, Alexander JS. Endothelial junctional protein redistribution and increased monolayer permeability in HUVECs isolated during preeclampsia. Am J Obstet Gynecol 2002;186:214–20.

    Article  CAS  Google Scholar 

  15. Brock TA, Gimbrone MA Jr. Platelet activating factor alters calcium homeostasis in cultured vascular endothelial cells. Am J Physiol 1986;250:H1086–92.

    Article  CAS  Google Scholar 

  16. Roberts JM, Redman CWG. Pre-eclampsia: More than pregnancy-induced hypertension. Lancet 1993;341:1447–51.

    Article  CAS  Google Scholar 

  17. Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:5–15.

    Article  CAS  Google Scholar 

  18. Wang Y, Walsh SW, Guo J, Zhang J. The imbalance between thromboxane and prostacyclin in preeclampsia is associated with an imbalance between lipid peroxides and vitamin E in maternal blood. Am J Obstet Gynecol 1991;165:1695–700.

    Article  CAS  Google Scholar 

  19. Hartung HP, Parnham MJ, Winkelmann J, Englberger W, Hadding U. Platelet activating factor (PAF) induces the oxidative burst in macrophages. Int J Immunopharmacol 1983;5:115–21.

    Article  CAS  Google Scholar 

  20. Droy-Lefaix MT, Drouet Y, Geraud G, Hosford D, Braquet P. Superoxide dismutase (SOD) and the PAF-antagonist (BN 52021) reduce small intestinal damage induced by ischemia-reperfusion. Free Radic Res Commun 1991;12–13(Part 2):725–35.

    Article  Google Scholar 

  21. Schwappach JR, Wood JG, Cheung LY. Superoxide dismutase attenuates effects of platelet-activating factor on gastric microcirculation. J Surg Res 1995;59:733–88.

    Article  CAS  Google Scholar 

  22. Huang YC, Nozik ES, Piantadosi CA. Superoxide dismutase potentiates platelet-avtivating factor-induced injury in perfused lung. Am J Physiol 1994;266:L246–54.

    CAS  PubMed  Google Scholar 

  23. Montrucchio G, Alloatti G, Camussi G. Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev 2000; 80:1669–99.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuping Wang MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, Y., Gu, Y., Lucas, M.J. et al. Antioxidant Superoxide Dismutase Attenuates Increased Endothelial Permeability Induced By Platelet-Activating Factor. Reprod. Sci. 10, 5–10 (2003). https://doi.org/10.1016/S1071-5576(02)00185-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/S1071-5576(02)00185-5

Key word

Navigation