Monocytes adhering by LFA-1 to placental syncytiotrophoblasts induce local apoptosis via release of TNF-alpha. A model for hematogenous initiation of placental inflammations.
Placental inflammations (villitis) are accompanied by loss of the syncytiotrophoblast, which is the cellular barrier separating maternal blood from fetal tissue in the villous placenta. We propose that syncytiotrophoblast loss is mediated by adhesion of activated maternal monocytes. This hypothesis was tested with a co-culture model of peripheral blood monocytes and placental syncytiotrophoblasts. We find that LPS-activated monocytes adhere to interferon-gamma (IFN-gamma)-treated syncytiotrophoblasts via monocyte LFA-1 for >48 h, during which time the monocytes induce trophoblast apoptosis and subsequent damage of the trophoblast layer. Optimal monocyte-mediated syncytiotrophoblast death requires both lipopolysaccharide (LPS) and IFN-gamma and is inhibited by either anti-tumor necrosis factor (TNF) antibody or epidermal growth factor. Syncytiotrophoblast damage is largely limited to culture surfaces in the vicinity of bound monocytes. These results show that activated maternal monocytes bound to the placental barrier can induce focal damage mediated by the inflammatory cytokine TNF-alpha and suggest a route for maternal leukocyte infiltration into the fetal stroma.
Garcia-Lloret
M I
MI
Department of Pediatrics, University of California, Los Angeles School of Medicine, USA.
Winkler-Lowen
B
B
Guilbert
L J
LJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion; D002824:Chorionic Villi / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D015726:Giant Cells; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D017154:Stromal Cells / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D007371:Interferon-gamma