Monocytes adhering by LFA-1 to placental syncytiotrophoblasts induce localapoptosis via release of TNF-alpha. A model for hematogenous initiation ofplacental inflammations

Placental inflammations (villitis) are accompanied by loss of the syncytiot rophoblast, which is the cellular barrier separating maternal blood from fe tal tissue in the villous placenta. We propose that syncytiotrophoblast los s is mediated by adhesion of activated maternal monocytes, This hypothesis was tested with a co-culture model of peripheral blood monocytes and placen tal syncytiotrophoblasts. We find that LPS-activated monocytes adhere to in terferon-gamma (IFN-gamma)-treated syncytiotrophoblasts via monocyte LFA-1 for > 48 h, during which time the monocytes induce trophoblast apoptosis an d subsequent damage of the trophoblast layer. Optimal monocyte-mediated syn cytiotrophoblast death requires both lipopolysaccharide (LPS) and IFN-gamma and is inhibited by either anti-tumor necrosis factor (TNF) antibody or ep idermal growth factor, Syncytiotrophoblast damage is largely limited to cul ture surfaces in the vicinity of bound monocytes. These results show that a ctivated 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.