Expression and Secretion of the Vascular Cell Adhesion Molecule-1 in Human Placenta and Its Decrease in Fetal Growth Restriction

Abstract

Objective: The vascular cell adhesion molecule-1 (VCAM-1) is a member of the immunoglobulin gene superfamily and is expressed principally on endothelial cells. The present study was undertaken to compare the expression and secretion of VCAM-1 from normal pregnancies and those complicated by fetal growth restriction (FGR).

Methods: Placentas from first-trimester (FT) (n = 17),normal term (n = 19), and FGR (n = 16) patients were collected immediately after elective cesarean delivery. VCAM-1 mRNA expression profiles by reverse transcriptase polymerase chain reaction, protein levels by enzyme-linked immunosorbent assay using explant culture in vitro, and its cellular localization by confocal microscopy were compared between FGR and normal placentas.

Results: Functionally active placental explants were used to detect immunoreactive VCAM-1 in conditioned media of all the samples from the three groups. The mean levels of VCAM-1 produced by FT villi were found to be 1.9-, 1.7-, and 1.5-fold higher (P < .02) than term villi at 24, 48, and 72 hours of culture, respectively. Conversely, the respective mean levels of VCAM-1 produced by FGR placental villi were 2.3-, 2.5-, and 2.0-fold lower than levels of the normal term placental villi (P < .05). The secretion profiles of VCAM-1 from FT, term, and FGR villi correlated well with the mRNA levels; the amount secreted in FT villi was twice that of term villi. Moreover, mRNA transcripts from FGR pregnancies showed significantly decreased expression, in conformity with explant results.

Conclusions: The presence of VCAM-1 in placental villi and down-regulation of its production at term indicate that VCAM-1 production is specific to developmental stage. The decreased VCAM-1 expression in FGR pregnancy could be attributed to the uteroplacental deficiency that is characteristics of this condition.

Keywords

Angiogenesis explant culture trophoblast RT-PCR

Get full access to this article

View all access options for this article.

References

1. Fisher SJ , Damsky CH . Human cytotrophoblast invasion. Semin Cell Biol 1993;4:183-188

2. Bischof P , Meisser A , Campana A . Mechanisms of endomentrial control of trophoblast invasion. J Reprod Fertil 2000;55(Suppl):65-71.

3. Chakraborty C , Gleeson LM , McKinnon T , Lala PK . Regulation of human trophoblast migration and invasiveness. Can J Physiol Pharmacol 2002;80:116-124.

4. Lyall F . The human placental bed revisited. Placenta 2002;23:555-562.

5. Hession C , Tizard R , Vassallo C , et al. Cloning of an alternate form of vascular cell adhesion molecule-1 (VCAM1). J Biol Chem 1991;266:6682-6685.

6. Imhof BA , Dunon D . Leukocyte migration and adhesion. Adv Immunol 1995;58:345-416.

7. Gearing AJ , Newman W . Circulating adhesion molecules in disease. Immunol Today 1993;14:506-512.

8. Banks RE , Gearing AJ , Hemingway IK , Norfolk DR , Perren TJ , Selby PJ . Circulating intercellular adhesion molecule-1 (ICAM-1), E-selection and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies. Br J Cancer 1993;68:122-124.

9. Koizumi A , Hashimoto S , Kobayashi T , Imai K , Yachi A , Horie T . Elevation of serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in bronchial asthma. Clin Exp Immunol 1995;101:468-473.

10.

10. Wellicome SM , Kapahi P , Mason JC , Lebranchu Y , Yarwood H , Haskard DO . Detection of a circulating form of vascular cell adhesion molecule-1: Raised levels in rheumatoid arthritis and systemic lupus erythematosus. Clin Exp Immunol 1993;92:412-418.

11.

11. Boldt J , Muller M , Heesen M , Neumann K , Hempelmann GG . Influence of different volume theapies and pentoxifylline infusion on circulating soluble adhesion molecules in critically ill patients. Crit Care Med 1996;24:385-391.

12.

12. Pigott R , Dillon LP , Hemingway IH , Gearing AJ . Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun 1992;187:584-589.

13.

13. Ryan DH , Nuccie BL , Abboud CN , Winslow JM . Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells. J Clin Invest 1991;88:995-1004.

14.

14. Freedman AS , Munro JM , Morimoto C , et al. Follicular non-Hodgkin's lymphoma cell adhesion to normal germinal centers and neoplastic follicles involves very late antigen-4 and vascular cell adhesion molecule-1. Blood 1992;79:206-212.

15.

15. Lyall F , Greer IA , Boswell f , Macara LM , Walker JJ , Kingdom JC . 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;101:485-487.

16.

16. Heyl W , Handt S , Reister F , et al. Elevated soluble adhesion molecules in women with pre-eclampsia. Do cytokines like tumour necrosis factor-alpha and interleukin-1beta cause endothelial activation. Eur J Obstet Gynecol Reprod Biol 1999;86:35-41.

17.

17. Bretelle F , Sabatier F , Blann A , et al. Maternal endothelial soluble cell adhesion molecules with isolated small for gestational age fetuses: Comparison with pre-eclampsia. Br J Obstet Gynecol 2001;108:1277-1282.

18.

18. Krauss T , Emons G , Kuhn W , Augustin HG . Predictive value of routine ciruclating soluble endothelial cell adhesion molecule measurements during pregnancy. Clin Chem 2002;48:1418-1425.

19.

19. Lyall F , Hayman RG , Ashworth JR , Duffie E , Baker PN . Relationship of cell adhesion molecule expression to endotheliumdependent relaxation in normal pregnancy and pregnancies complicated with preeclampsia or fetal growth restriction. J Soc Gynecol Investig 1999;6:196-201.

20.

20. Kliman HJ , Feinberg RF , Haimowitz JE . Human trophoblast endothelial interactions in an in vitro suspension culture system. Placenta 1990;11:349-367.

21.

21. Rajashekhar G , Loganath A , Roy AC , Wong YC . Expression and localization of angiogenin in plancenta: Enhanced levels at term over first trimester villi. Mol Reprod Dev 2002;62:159-166.

22.

22. Ali S , Kaur J , Patel KD . Intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and regulated on activation normal T cell expressed and secreted are expressed by human breast carcinoma cells and support eosinophil adhesion and activation. Am J Pathol 2000;157:313-321.

23.

23. Polte T , Newman W , Gopal TV . Full length vascular cell adhesion molecule 1 (VCAM-1). Nucleic Acids Res 1990;18:5901-5901.

24.

24. Djurovic S , Schjetlein R , Wisloff F , Haugen G , Berg K . Increased levels of intercellular adhesion molecules and vascular cell adhesion molecules in pre-eclampsia. Br J Obstet Gynaecol 1997;104:466-470.

25.

25. Phocas I , Rizos D , Papoulias J , Xyni K , Sarandakou A , Salamalekis E . A comparative study of serum soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 in preeclampsia. J Perinatol 2000;20:114-119.

26.

26. Zygmunt M , Boving B , Wienhard J , et al. Expression of cell adhesion molecules in the extravillous trophoblast is altered in IUGR. Am J Reprod Immunol 1997;38:295-301.

27.

27. Zhou Y , Damsky CH , Fisher SJ . Pre-eclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome? J Clin Invest 1997;99:2152-2164.

28.

28. Damsky CH , Fitzgerald M , Fisher SJ . Distribution patterns of extra cellular matrix components and adhesion receptors are intrinsically modulated during first trimester cytotrophoblast differentiation along the invasive pathway, in vivo. J Clin Invest 1992;89:210-222.

29.

29. Damsky CH , Sutherland AE , Fisher SJ . Adhesive interactions in early mammalian embryogenesis, implantation and placentation. FASEB J 1993;7:1320-1328.

30.

30. Damsky CH , Librach C , Lim KH , et al. Integrin switching regulates normal trophoblast invasion. Development 1994;120:3657-3666.

31.

31. Alexander C , Werb Z . Extra cellular matrix degradation. In: Hay ED , ed. Cell biology of extra cellular matrix. New York: Plenum Press, 1991;255-302.

32.

32. Raynor BD , Parthasarathy S . Maternal serum vascular cell adhesion molecule concentration during pregnancy. J Soc Gynecol Investig 1997;4:78-80.

33.

33. Johnson MR , Anim-Nyame N , Johnson P , Sooranna SR , Steer PJ . Does endothelial cell activation occur with intrauterine growth restriction? Br J Obstet Gynecol 2002;109:836-839.

34.

34. Zhou Y , Fisher SJ , Janatpour M , et al. Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion? J Clin Invest 1997;99:2139-2151.

35.

35. Jaakkola K , Jokimaa V , Kallajoki M , Jalkanen S , Ekholm E . Pre-eclampsia does not change the adhesion molecule status in the placental bed. Placenta 2000;21:133-141.

36.

36. Tziotis J , Malamitsi-Puchner A , Vlachos G , Creatsas G , Michalas S . Adhesion molecules expression in the placental bed of pregnancies with pre-eclampsia. Br J Obstet Gynecol 2002;109:197-201.

37.

37. Lyall F , Greer IA , Boswell F , Young A , Macara LM , Jeffers MD . Expression of cell adhesion molecules in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth retardaton. Placenta 1995;16:579-587.

38.

38. Koch AE , Halloran MM , Haskell CJ , Shah MR , Polverini PJ . Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 1995;376:517-519.

39.

39. William C , Schindler R , Frei U , Eckardt KU . Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells. Am J Physiol 1999;276:H2044-H2052.

40.

40. Sebire NJ , Talbert D . “Cor placentale”: placental intervillus/intravillus blood flow mismatch is the pathophysiological mechanism in severe intrauterine growth restriction due to uteroplacental disease. Med Hypotheses 2001;57:354-357.