WCRB2014 POSTER PRESENTATIONS (1) (335 abstracts)
Effect of pentraxin 3 on inflammation-induced fetal loss
Rita Bonfiglio 1 , Antonella Camaioni 1 , Francesca Palone 1 , Barbara Bottazzi 2 , Marina Sironi 2 , Cecilia Garlanda 2 , Giovanni Salvatori 3 , Alberto Mantovani 2 & Antonietta Salustri 1
1University of Rome Tor Vergata, Rome, Italy; 2Humanitas Clinical and Research Center, Milan, Italy; 3Sigma-tau Industrie Farmaceutiche Riunite S.p.A, Rome, Italy.
Pentraxin 3 (PTX3) is an essential component of the innate immunity with a non-redundant role in conferring resistance to pathogens and in modulating inflammatory reactions in several diseases. Pregnancy is characterized by mild systemic immunosuppression and inflammation. An uncontrolled immune activation at the fetal–maternal interface caused by bacterial infections or inflammatory stimuli is associated with high risk of miscarriage both in mice and in women. In this study, we investigated the effect of the administration of recombinant human-PTX3 (rhPTX3) on a lipopolysaccharide (LPS)-caused early fetal loss model.
Pregnant 129/sv mice were treated at 9.5 dpc with LPS ± full length rhPTX3, or the rhN-terminal or rhC-terminal domain PTX3 and sacrificed at 13.5 dpc to assess the embryonic resorption rate. Circulating levels of TNF-α and IL10 and decidual levels of rhPTX3 were measured at 1.5 h post-treatment by ELISA.
We found that the administration of rhPTX3 significantly improved pregnancy success reducing the percentage of LPS-induced fetal loss from 70 to 35%. The rhC-terminal domain, but not the rhN-terminal domain, mimicked the action of the full length protein, indicating that the protective role played by PTX3 is exclusively exerted by its pentraxin domain. The circulating levels of TNF-α and IL10, key players in mediating and inhibiting the LPS-induced abortion, respectively, were not altered by rhPTX3. Noteworthy, the administered rhPTX3 efficiently penetrated into the decidua. These results suggest that PTX3 is able to rescue embryos from the adverse effects of LPS by acting at the local level.
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ISSN 2052-1472 (online)
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