Surfactant protein A suppresses preterm delivery induced by live Escherichia coli in mice

Biol Reprod. 2018 Sep 1;99(3):546-555. doi: 10.1093/biolre/ioy074.

Abstract

Preterm birth accounts for the majority of neonatal morbidity and mortality in the developed world. A significant proportion of cases of spontaneous preterm labor are attributable to infections within gestational tissues. Surfactant protein A (SP-A), a collectin produced in the fetal lung and other tissues, has been shown previously in mice to suppress preterm delivery due to intrauterine (IU) instillation of sterile proinflammatory substances. Here we report a powerful antilabor effect for SP-A after IU infection with live Escherichia coli. SP-A abolished preterm birth (rate reduced from 100% to 0%) when it was administered into the uterus simultaneously with bacterial infection, reducing it by 75% when administered intravenously at the same time as IU bacterial inoculation, and by 48% when administered intravenously 4 h after IU bacterial infection. This effect on preterm delivery was accompanied by a parallel benefit on fetal survival in utero. SP-A had no effect on bacterial growth but reversed several major consequences of infection, including increased production of inflammatory mediators and a shift in macrophage polarization to the M1 phenotype. These findings suggest that exogenous SP-A has potential use to counteract infection-induced labor by reversing its proinflammatory consequences.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Animals
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Escherichia coli Infections / complications*
  • Female
  • Inflammation / prevention & control
  • Macrophages / drug effects
  • Macrophages / physiology
  • Mice
  • Pregnancy
  • Premature Birth / microbiology*
  • Premature Birth / prevention & control*
  • Pulmonary Surfactant-Associated Protein A / administration & dosage*
  • Uterus / drug effects

Substances

  • Pulmonary Surfactant-Associated Protein A