Document Detail

Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women.
MedLine Citation:
PMID:  11502865     Owner:  NLM     Status:  MEDLINE    
Impaired invasion of uteroplacental arteries by extravillous trophoblast cells is a key pathogenic mechanism of preeclampsia. We previously demonstrated that reduced trophoblast invasion into uteroplacental spiral arteries was associated with an excess of macrophages in and around these arteries. To explore the significance of these observations, we correlated the extent of extravillous trophoblast apoptosis in placental bed biopsy specimens with macrophage distribution and studied the effect of macrophages upon trophoblast apoptosis in vitro. Extravillous trophoblast hybrid cells were cocultured with activated macrophages exposed to exogenous tumor necrosis factor alpha (TNFalpha), anti-tumor necrosis factor receptor I (TNF-RI), and tryptophan depletion, and the rates of trophoblast apoptosis were measured. Extravillous trophoblast hybrid cells showed increased rates of apoptosis following exposure to exogenous TNFalpha, with tryptophan depletion, and when cocultured with activated macrophages. The proapoptotic effects of macrophages in vitro were completely inhibited only by simultaneous addition of tryptophan and anti-TNF-RI. Our data indicate that macrophages, residing in excess in the placental bed of preeclamptic women, are able to limit extravillous trophoblast invasion of spiral arterial segments through apoptosis mediated by the combination of TNFalpha secretion and tryptophan depletion. The mechanisms by which macrophages are activated and recruited to the placental bed are presently unknown but are likely central to the pathogenesis of preeclampsia.
F Reister; H G Frank; J C Kingdom; W Heyl; P Kaufmann; W Rath; B Huppertz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  81     ISSN:  0023-6837     ISO Abbreviation:  Lab. Invest.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-14     Completed Date:  2001-09-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1143-52     Citation Subset:  IM    
Department of Obstetrics and Gynecology, University of Technology, Aachen, Germany.
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MeSH Terms
Antigens, CD
Arteries / pathology
Endothelium, Vascular / pathology
Hybrid Cells
Macrophages / physiology*
Models, Biological
Placenta / blood supply
Pre-Eclampsia / etiology*,  pathology*
Receptors, Tumor Necrosis Factor / antagonists & inhibitors
Receptors, Tumor Necrosis Factor, Type I
Trophoblasts / metabolism,  pathology*
Tryptophan / metabolism
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / pharmacology
Uterus / pathology*
Reg. No./Substance:
0/Antigens, CD; 0/Receptors, Tumor Necrosis Factor; 0/Receptors, Tumor Necrosis Factor, Type I; 0/Tumor Necrosis Factor-alpha; 73-22-3/Tryptophan

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