Roles of surfactant proteins, SP-A and SP-D, in pregnancy and parturition

Abstract

Surfactant proteins SP-A and SP-D are important key molecules responsible for pulmonary homeostasis and innate immunity against infectious pathogens. SP-A and SP-D are also found in various parts of the placenta as well as amniotic fluid. The levels of these proteins in the amniotic fluid are good biomarkers of fetal lung maturation. The development of the lungs in fetal growth is important for fetal survival in extrauterine life. In pregnant mice models, a huge increase in SP-A and SP-D levels in the amniotic sac has been reported close to parturition suggesting an important role of these proteins in the hormonal pathway to labour. In this thesis, full length natural and recombinant proteins of human SP-A and SP-D were generated and examined on the maternal-fetal tissues of the placenta (explants of amnion, chorion and decidua) under inflammatory conditions. A range of innate and adaptive immune markers and prostaglandin targets were examined to show that SP-A and SP-D modulate the prostaglandin pathway. Thus, an imbalance in this could potentially lead to disorders such as intrauterine growth retardation and preeclampsia. The cellular basis of immune regulation and prostaglandin pathway was also examined via fractionation of decidual macrophages. Curiously, SP-A and SP-D appears to suppress pro-inflammatory response of decidual macrophages after challenging with LPS. This thesis thus divulges specific and mutually inclusive functions of SP-A and SP-D in the maintenance of pregnancy, protection against intrauterine infection, dampening of inflammation, and premature activation of parturition.