362 - Disruption of the SP-R210L Isoform of the Surfactant Protein A receptor in macrophages delays chorioamnionitis-induced premature delivery in mice

Poster Number: 362
Publication Number: 362.440

Brandon Worth, Penn State Children's Hospital, Hershey, PA, United States; Zissis C. Chroneos, Pennsylvania State University College of Medicine, Hershey, PA, United States; Kim K. Doheny, Penn State Health Children's Hospital/Penn State College of Medicine, Hershey, PA, United States; Jennifer L. Booth, Penn State College of Medicine, Hershey, PA, United States; Todd M. Umstead, Pennsylvania State University College of Medicine, Hershey, PA, United States

Background: Intrauterine infection plays a significant role in the morbidity and mortality associated with prematurity. Surfactant Protein-A (SP-A) is well known to have an anti-inflammatory effect and has been shown to reduce preterm delivery without significant increase in mortality in mouse studies. SP-R210 is an SP-A receptor present on macrophages that assists with phagocytosis of infectious sources to decrease susceptibility to pulmonary infections. SP-A and SP-R210 are expressed in many tissues, including reproductive tissues and the amnion. SP-R210 has two isoforms; SP-R210L and SPR210S in various macrophage subsets.

Objective: We are studying the role of the SP-R210L isoform in chorioamnionitis induced premature delivery using transgenic mice with conditional deletion of SP-R210L in macrophages.

Design/Methods: Mice were divided into a case-control study involving timed pregnant wild type (WT) and SPR-210L-deficient knockout (KO) mice at 15.5 and 18.5 days post coitus (pc). Chorioamnionitis was induced by ultrasound guided injections with 10 µg of lipo-Polysaccharide (LPS) from Escherichia coli strain O111:B4 under anesthesia and mice were monitored following injection for time to parturition.

Results: In WT mice (n=3), the time to premature delivery was 17.6±1.5 hours, whereas SP-R210L-deficient (n=3) mice delivered significantly later, at 22.0±2.6 hours after LPS injection (p=0.070). Conclusion(s): These preliminary results indicate that SP-R210L contributes to premature parturition and is crucially involved in the intrauterine inflammatory response to infection. Although the small number of mice is a limitation of this study, the results warrant further investigation into the role SP-SP-R210 isoform in the pathophysiology of chorioamnionitis. Validation of these early results could lead to novel treatments to reduce the risk of premature delivery as a result of chorioamnionitis.
Disruption of the SP-R210L Isoform of the Surfactant Protein A receptor in macrophages delays chorioamnionitis-induced premature delivery in miceBrandon Worth CV 10.25.21.pdf