A Signal from Surfactant

Science's STKE  13 Apr 2004:
Vol. 2004, Issue 228, pp. tw130-TW130
DOI: 10.1126/stke.2282004TW130

Condon et al. uncovered a new role for lung surfactant as a signal whereby a developing fetus announces that it's ready for birth. Labor that starts too early or too late can endanger the fetus. For example, premature infants are at risk of respiratory distress syndrome, a serious condition that results from a lack of surfactant in the immature lung. Labor is associated with an inflammatory response, in which leukocytes infiltrate the myometrium, but the initiating stimulus and source of these leukocytes--as well as the trigger for labor--have remained unclear. Condon et al. found that secretion of surfactant protein A (SP-A) mRNA in mouse amniotic fluid (AF) increased late in gestation along with production of interleukin-1β (IL-1β, a marker for activation) in AF macrophages and the number of macrophages in the uterine wall. The authors used wild-type mice carrying transgenic embryos to demonstrate that at least some of these uterine macrophages were of fetal origin. Intra-amniotic injection of SP-A promoted migration of fetal macrophages into the uterine wall and caused preterm labor, whereas intra-amniotic injection of antibodies to SP-A delayed labor. SP-A stimulated the expression of IL-1β and nuclear factor κB (NF-κB) in macrophages isolated from AF. NF-κB p50 and p65 proteins redistributed from uterine cytoplasm to nucleus late in gestation, an effect that was mimicked by intra-amniotic injection of SP-A. Intra-amniotic injection of an NF-κB inhibitor delayed the onset of labor and prevented premature labor in response to SP-A. Thus, the authors propose that SP-A from fetal lung acts as a labor-initiating signal to the myometrium of fetal maturity.

J. C. Condon, P. Jeyasuria, J. M. Faust, C. R. Mendelsohn, Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition. Proc. Natl. Acad. Sci. U.S.A. 101, 4978-4983 (2004). [Abstract] [Full Text]