512: Evidence for participation of the acute phase reactive protein haptoglobin (Hp) in pathophysiologic events related to preterm birth (PTB)

reactive protein haptoglobin (Hp) in pathophysiologic events related to preterm birth (PTB) Megan McCarthy, John Hardy, Antonette Dulay, Christine Laky, Ramesha Papanna, Catalin Buhimschi, Irina Buhimschi Yale University, Ob/Gyn & Reprod. Sci., New Haven, CT OBJECTIVE: Hp plays key immunoregulatory roles. Its gene is polymorphic with evidence of functionally distinct phenotypes (Hp1-1, Hp2-1, Hp2-2). Fetal Hp is not expressed in utero unless an inflammatory response to infection is triggered. Given that in sepsis Hp has a vascular endothelial prostaglandin (PG) inhibitory effect, we hypothesized that when expressed, fetal Hp modulates placental biosynthesis of PG and matrix metalloproteinases (MMPs) and that this effect is phenotype dependent. STUDY DESIGN: Placentas from pregnancies complicated by PTB (n 11, GA: 26 3wks) were immunostained and scored for intensity of Hp expression. Histological chorioamnionitis (HCA) was present in 6 of 11 cases. Placental Hp gene expression was evaluated by RTPCR. Cord blood was obtained in all cases, and fetal Hp switch-on and phenotype status was determined by Western blotting. A villous trophoblast explant system (term elective CS, n 5) was used to investigate the effect of Hp phenotypes 1-1 and 2-2 on PGE2 and MMP9 biosynthesis in the presence and absence of LPS (50 ng/mL). Hp dose (10 ug/mL) mimicked fetal circulating level when exposed to infection. HEK-Blue LPS Detection Kit ruled-out LPS contamination of purified Hp. PGE2 and MMP9 were quantified by ELISA. RESULTS: There was positive Hp immunoreactivity within the vascular fetal spaces of all cases with HCA (n 6). There was no significant difference in the Hp gene expression level between placentas with and without HCA. In vitro, in the absence of LPS, Hp1-1 did not alter the release of PGE2 or MMP9, while Hp 2-2 exhibited an inhibitory effect (P .05). In the presence of LPS both Hp phenotypes upregulated PGE2 release (2-fold over the LPS level, P .05), while MMP9 biosynthesis remained unaffected. CONCLUSION: We provide evidence that in the presence of endotoxin, Hp stimulates placental PGE2 biosynthesis in a phenotype-specific manner, implying that this protein could play a role in infectioninduced PTB.