Expanded role of the surfactant system in perinatal transition

The role of surfactant as an etiological factor of RDS is well known. Besides the surface activity, several components of the surfactant are involved in the innate immunity. The fact that surfactant is secreted into the amniotic fluid makes it as an interesting candidate that influences the premature birth, particularly in pregnancies complicated by chorioamnionitis. Surfactant associated collectins, surfactant protein A (SP-A) and SP-D are well known proteins that bind several microbes, influence phagocytosis by alveolar macrophages, and have proand anti-inflammatory roles. We have studied the roles of lung collectins using two approaches: 1. transgenic mice expressing either SP-A or SP-B are studied in the setting of LPS-induced preterm birth; 2. the association of SP-A and SP-D polymorphism with the susceptibility to preterm birth is studied. Preliminary results are presented. In addition new results on the role of SP-C in preterm birth are shown. According to preliminary evidence certain SP-C gene (SFTPC) polymorphisms associate with lung diseases and very preterm birth (Lahti et al. Eur J Hum Gen 2004;12:312-20). Aims: We investigated the association of SFTPC single nucleotide polymorphism (SNP) rs4715 with factors affecting spontaneous preterm birth and characterized the SP-C expression in human and mouse gestational tissues. Methods: SFTPC SNP rs4715 polymorphism was genotyped in a homogeneous Northern European population of mothers and infants in spontaneous preterm birth and term controls. The expression and protein of SP-C in gestational tissues was analyzed. Results: SFTPC SNP rs4715 did not associate with spontaneous preterm birth. However, fetuses with short interval (< 72 hours) between preterm premature rupture of fetal membranes (PPROM) and preterm birth had significant overrepresentation of the minor allele A, whereas in fetuses with prolonged PPROM (≥ 72 hours) the frequency was decreased (P<0.0001). Maternal SFTPC did not associate with the duration of PPROM. SP-C mRNA and proprotein were detected in fetal membranes, placenta, and pregnant uterus. Conclusion: SFTPC SNP rs4715 associates with the duration of PPROM and SP-C is expressed in gestational tissues. We propose that fetal SFTPC either moderates the inflammatory activation or serves as an antimicrobial peptide protecting the extraembryonic compartment.