"Women who go into preterm labor frequently have an infection of the membranes that surround the fetus, and the number of macrophages in the wall of the uterus increases with the initiation of preterm labor. When women go into labor at term, they also have an increase in macrophages in the uterus," Dr. Mendelson said.
This led the researchers to investigate whether there was a connection between what happens during normal labor at term and in infected mothers who go into early labor.
"This also raised the question: If bacterial infection can cause increased macrophage infiltration of the uterus in preterm labor, what is the signal for the enhanced macrophage migration to the uterus at term?" Dr. Mendelson said.
In mice, the developing fetal lung starts producing SP-A at 17 days gestation; full-term delivery occurs at 19 days. The developing human fetus starts producing SP-A in increasing amounts after 30 to 32 weeks of a 40-week normal gestation, at which time the baby's lungs are essentially developed. As the fetus "breathes" amniotic fluid in the womb, the protein is released into the fluid.
"The SP-A protein binds to macrophages in the amniotic fluid, macrophages that come from the fetus itself," said Dr. Jennifer Condon, a postdoctoral researcher in biochemistry and the study's lead author.
The macrophages, "activated" by the protein, make their way through the amniotic fluid to the wall of the uterus. Once embedded there, they produce a chemical that stimulates an inflammatory response in the uterus, ultimately leading to labor.
The researchers also found that injecting a pregnant mouse with SP-A before day 17 of the pregnancy caused the mouse to deliver early. Injection of pregnant mice with an antibody that blocks SP-A function caused them to deliver late.
Identifying the receptors on the macrophages
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Contact: Amanda Siegfried
Amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
22-Mar-2004