Skip to main content
SpringerLink
Log in

Activation of Endothelial Cells in Preeclampsia: Increased Neutrophil-Endothelial Adhesion Correlates With Up-regulation of Adhesion Molecule P-selectin in Human Umbilical Vein Endothelial Cells Isolated From Preeclampsia

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

Abstract

Objective

Increased endothelial activation has been suggested to be important in the pathophysiology for preeclampsia. Our objective was to examine whether in preeclampsia neutrophil adherence to endothelial cells is increased and whether endothelial cell-surface adhesion molecule expression is up-regulated.

Methods

Endothelial cells were isolated from normal (n = 10) and preeclamptic (n = 9) human umbilical veins (HUVECs). Neutrophils were isolated from normal, healthy, nonpregnant female volunteers. Freshly isolated neutrophils were labeled with 51Cr, and labeled neutrophils were coincubated with confluent normal and preeclamptic endothelial monolayers. Adhesion assays were then performed. To determine whether in preeclampsia endothelial cellular-surface adhesion molecules are responsible for increased neutrophil-endothelial adhesion, cellular adhesion molecule expression of P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin were examined by an enzyme-linked binding assay. Furthermore, adhesion assays were also performed on HUVECs pretreated with antibodies against P-selectin, ICAM-1, VCAM-1, and E-selectin.

Results

Neutrophil adhesion to the HUVECs from preeclamptic pregnancies was significantly increased compared with neutrophil adhesion to the HUVECs from normal pregnancies (P < .01). Expression of cellular-surface adhesion molecule of P-selectin was significantly higher (P < .01) and ICAM-1 was significantly lower (P < .05) in HUVECs isolated from preeclampsia than from normal controls, whereas there was no difference for VCAM-1 and E-selectin expression between HUVECs from normal and preeclamptic pregnancies. No differences were found for neutrophil-endothelial adhesion on normal HUVECs pretreated with anti-P-selectin, anti-ICAM-1, anti-VCAM-1, and anti-E-selectin compred with the untreated cells. However, pretreatment of preeclampsia HUVECs with anti-P-selectin, anti-ICAM-1, anti-VCAM-1, and anti-E-selectin completely or partially blocked the neutrophil-endothelial adhesion compared to the untreated cells.

Conclusion

There is a significant increase in neutrophil adhesion to HUVECs that are isolated from preeclamptic pregnancies compared with normal controls. This increase appears to be a result of up-regulation of the cell-surface adhesion molecule P-selectin. Elevated P-selectin expression may play a significant role in neutrophil-endothelial hyperadhesiveness and contribute to vascular complications associated with preeclampsia.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  2. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: An endothelial cell disorder. Am J Obstet Gynecol 1989; 161: 1200–4.

    Article  CAS  Google Scholar 

  3. Giugliano D, Cenello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996; 19: 257–67.

    Article  CAS  Google Scholar 

  4. 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 

  5. Lewis PJ, Shepherd GI, Ritter J, et al. Prostacyclin and preeclampsia. Lancet 1981; 1(8219): 559.

    Article  CAS  Google Scholar 

  6. McCarthy AL, Woolfson RG, Raju SK, Poston L. Abnormal endothelial cell function of resistance arteries from women with preeclampsia. Am J Obstet Gynecol 1993; 168: 1323–30.

    Article  CAS  Google Scholar 

  7. Taylor RN, Crombleholme WR, Friedman SA, Jones LA, Casal DC, Roberts JM. High plasma cellular fibronectin levels correlate with biothemical and clinical features of preeclampsia but cannot be attributed to hypertension alone. Am J Obstet Gynecol 1991; 165: 895–901.

    Article  CAS  Google Scholar 

  8. Lyall F, Greer IA, Boswell F, Macara LM, Walker JJ, Kingdom JCP. The cell adhesion molecule, VCAM-1, is selectively elevated in serum in pre-eclampsia: Does this indicate the mechanism of leucocyte activation? Br J Obstet Gynaecol 1994; 101: 485–7.

    Article  CAS  Google Scholar 

  9. Krauss T, Kuhn W, Lakoma C, Augustin HG. Circulating en-dothelial cell adhesion molecules as diagnostic markers for the early identification of pregnant women at nsk for development of preeclampsia. Am J Obstet Gynecol 1997; 177: 443–9.

    Article  CAS  Google Scholar 

  10. 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 

  11. Ichikawa H, Wolf RE, Aw TY, et al. Exogenous xanthine promotes neutrophil adherence to cultured endothelial cells. Am J Physiol 1997; 273: G342–7.

    CAS  PubMed  Google Scholar 

  12. Markert M, Andrews PC, Babior BM. Measurement of O2 production by human neutrophils: The preparation and assay of NADPH oxidase-containing particles from human neutrophils. Methods Enzymol 1984; 105: 358–65.

    Article  CAS  Google Scholar 

  13. Ohno N, Ichikawa H, Coe L, Kvietys PR, Granger DN, Alexander JS. Soluble selectins and ICAM-1 modulate neutrophil-endothehal adhesion and diapedesis m vitro. Inflammation 1997; 21: 313–24.

    Article  CAS  Google Scholar 

  14. Khan BV, Parthasarathy SS, Alexander RW, Medford RM. Modified low-density lipoprotein and its constituents augment cytokme-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells. J Clin Invest 1995; 95: 1262–70.

    Article  CAS  Google Scholar 

  15. Kupfenninc MJ, Peaceman AM, Wigton TR, Rehnberg KA, Socol ML. Tumor necrosis factor-a is elevated in plasma and amniotic fluid of patients with severe preeclampsia. Am J Obstet Gynecol 1994; 170: 1752–9.

    Article  Google Scholar 

  16. Vince GS, Starkey PM, Austgulen R, Kwiatkowski D, Redman CWG. Interleukin-6, tumour necrosis factor and soluble tumour necrosis factor receptors in women with pre-eclampsia. Br J Obstet Gynaecol 1995; 102: 20–5.

    Article  CAS  Google Scholar 

  17. Okayama N, Ichikawa H, Coe L, Itoh M, Alexander JS. Exogenous nitric oxide enhances hydrogen peroxide-mediated neutrophil adherence to cultured endothelial cells. Am J Physiol 274(5): L820–6.

  18. Gamble JR, Harlan JM, Klcbanoff SJ, Vadas MA. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci USA 1985; 82: 8667–71.

    Article  CAS  Google Scholar 

  19. Paidas MJ, Dijkstra K, Salafia CM, et al. Elevated levels of plasma P-selectin and found in women destinated to develop preeclampsia (PE) (abstract). Proceedings of the 45th Annual Meeting of Society for Gynecologic Investigation, Adanta, Georgia, 1998; 131A.

  20. Bcvilacqua MP. Endothelial-leukocyte adhesion molecules. Ann Rev Immunol 1993; 11: 767–804.

    Article  Google Scholar 

  21. Bochner BS, Luscinskas FW, Gimbrone MA, et al. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1—activated human vascular endothelial cells: Contributions of endothelial cell adhesion molecules. J Exp Med 1991; 173: 1553–6.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, and Physiology, Louisiana State University Medical Center, P.O. Box 33932, Shreveport, Louisiana, 71130, USA

    Yuping Wang MD, PhD, C. David Adair MD, Laura Coe MS, Jonathan W. Weeks MD, David F. Lewis MD & J. Steven Alexander PhD

Authors
  1. Yuping Wang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. David Adair MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura Coe MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jonathan W. Weeks MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David F. Lewis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Steven Alexander PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuping Wang MD, PhD.

Additional information

Supported partially by the Edward P. Stile Trust Fund at Louisiana State University Medical Center in Shreveport.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Y., Adair, C.D., Coe, L. et al. Activation of Endothelial Cells in Preeclampsia: Increased Neutrophil-Endothelial Adhesion Correlates With Up-regulation of Adhesion Molecule P-selectin in Human Umbilical Vein Endothelial Cells Isolated From Preeclampsia. Reprod. Sci. 5, 237–243 (1998). https://doi.org/10.1177/107155769800500503

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/107155769800500503

Key words

Search

Navigation