OS006. Functional expression of endogenous ligands of XXXX on monocytes and placentae from @entity1 during normal pregnancy andpre-eclampsia.

@entity1 @entity518 @entity2002 @entity650 @entity1356 @entity310 @entity31847 @entity1003 @entity1468 @entity2939 @entity687 @entity688 @entity597
INTRODUCTION: @entity1468 ( @entity1468 ) is characterized by an exaggerated systemic inflammatory response (ESIR). Several recent studies by our group and others have demonstrated up-regulation of @entity2939 ( @entity2939 ) in trophoblast, placenta and leukocytes in @entity1468 but the exact role of @entity2939 in the pathogenesis of @entity1468 remains unclear. OBJECTIVES: We sought to determine the expression levels of endogenous ligands of @entity2939 in plasma and placentas from @entity1 with @entity1468 vs normotensive pregnant @entity1 (NP), and to compare the inflammatory cytokine expression profiles of monocytes from @entity1 with @entity1468 to NP, in order to identify which of these endogenous ligands of @entity2939 may play a functional role in the pathogenesis of @entity1468 for further study. METHODS: We recruited 16 @entity1468 (gestational age=33.6  3.0weeks), 10 normal pregnant (gestational age=31.6  3.8weeks) and 10 non-pregnant @entity1 . Plasma levels of endogenous @entity2939 ligands-heparan @entity597 , hyaluronan, fibronectin, @entity2002 and @entity518 ( @entity518 )-were measured by ELISA. Monocytes were isolated from peripheral blood, cultured and stimulated by lipopolysaccharide (LPS; @entity2939 bacterial ligand) and endogenous @entity2939 ligands, and inflammatory cytokines were measured in supernatant medium by cytometric array. Placental tissue from @entity1468 and NP were investigated for the different endogenous ligands by immunohistochemistry. RESULTS: Plasma levels of @entity31847 and fibronectin did not differ between study groups, but @entity518 was higher in @entity1468 (P<0.05) whilst @entity2002 was significantly lower in @entity1468 compared to NP (P<0.05). Stimulation of @entity1468 monocytes with LPS resulted in profound secretion of various cytokines: @entity650 , @entity687 , @entity1356 , @entity310 and @entity688 , in comparison with NP. Moreover, exposure to @entity2002 , but not to other endogenous @entity2939 ligands, was also associated with significantly increased production of inflammatory cytokines in @entity1468 compared to NP. Also, we observed altered distribution levels of studied endogenous ligands in the placenta from @entity1468 vs NP. CONCLUSION: Our findings of increased inflammatory cytokine expression levels in @entity1468 in response to LPS are consistent with upregulation of @entity2939 in @entity1468 . A similar response induced by @entity2002 suggests an important role for this endogenous ligand of @entity2939 in the pathogenesis of @entity1468 . Whether our observation of decreased plasma levels of @entity2002 in @entity1468 is linked to this observation, or represents increased fibrinogenesis and fibrinolysis associated with the @entity1003 seen in this condition, is unclear.
