Abstract
The Fas-Fas ligand (FasL) pathway of apoptosis is abnormally activated in diseases associated with impaired immune tolerance or chronic inflammation. Pregnancy-related hypertension is a spectrum of disease that commonly causes significant morbidity in women and in their newborn infants, is associated with generalized inflammation, and may be causally related to impaired maternal-fetal tolerance. Our recent observation of enhanced trophoblast expression of FasL in one form of pregnancy-related hypertension led us to hypothesize that this group of disorders might be associated with abnormal activation of the Fas-FasL pathway. To test this hypothesis, we prospectively quantified soluble and leukocyte-associated Fas receptor and FasL in the maternal and umbilical cord blood (CB) sera of 20 gestations complicated by preeclampsia and of 18 normal control gestations, using ELISA and flow cytometric analyses. We determined higher soluble FasL levels in paired maternal and CB sera of hypertensive gestations compared with control gestations (p < 0.01); in contrast, soluble Fas levels were similar between groups. Surface expression of FasL was lower on maternal (p < 0.01) and CB (p < 0.05) neutrophils from affected gestations, whereas surface Fas expression was lower on maternal (p < 0.02), but not CB, neutrophils and lymphocytes. We conclude that expression of Fas and FasL in sera and on leukocytes is altered in gestations complicated by preeclampsia, and speculate that activation of the Fas-FasL pathway mediates associated pathologic processes in affected women and in their neonates.
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Abbreviations
- CB:
-
umbilical cord blood
- CS:
-
cesarean section
- FasL:
-
Fas ligand
- MMP:
-
matrix metalloproteinase
- PIH:
-
pregnancy-induced hypertension
- sFas:
-
soluble Fas
- sFasL:
-
soluble Fas ligand
- SGA:
-
small-for-gestational age
- TNF-α:
-
tumor necrosis factor-α
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Acknowledgements
The authors thank the Labor and Delivery nurses and physicians at Shands-University of Florida for their help in identifying study subjects and in collecting maternal and CB samples. We also thank Drs. Nasser Chegini and Cynthia Edstrom for their helpful comments and review of this manuscript.
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Supported partly from funds provided by The Children's Miracle Network Telethon, STOP! Children's Cancer, Inc., and the Howard Hughes Medical Institute Research Resources Program.
Presented in part at the annual meeting of the Society for Pediatric Research, Boston, MA, U.S.A., May 14, 2000.
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Kuntz, T., Christensen, R., Stegner, J. et al. Fas and Fas Ligand Expression in Maternal Blood and in Umbilical Cord Blood in Preeclampsia. Pediatr Res 50, 743–749 (2001). https://doi.org/10.1203/00006450-200112000-00019
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DOI: https://doi.org/10.1203/00006450-200112000-00019
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