Epithelial Cell-Derived Neutrophil-Activating Peptide-78 Is Present in Fetal Membranes and Amniotic Fluid at Increased Concentrations with Intra-amniotic Infection and Preterm Delivery

• Published in: Biology of reproduction Vol. 70; no. 1; pp. 253 - 259
• Main Authors: KEELAN, J. A, YANG, J, ROMERO, R. J, CHAIWORAPONGSA, T, MARVIN, K. W, SATO, T. A, MITCHELL, M. D
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-01-2004
• Subjects: Amniotic Fluid - metabolism; Biological and medical sciences; Cells, Cultured; Chemokine CXCL5; Chemokines, CXC; Chorioamnionitis - metabolism; Epithelial Cells - cytology; Epithelial Cells - metabolism; Extraembryonic Membranes - cytology; Extraembryonic Membranes - metabolism; Female; Fundamental and applied biological sciences. Psychology; Humans; Infant, Newborn; Infant, Premature; Interleukin-8 - analogs & derivatives; Interleukin-8 - metabolism; Mammalian male genital system; Morphology. Physiology; Pregnancy; Pregnancy Complications, Infectious - metabolism; Uterus - cytology; Uterus - metabolism; Vertebrates: reproduction; Infection; Peptides; Fetal membrane; Amniotic fluid; Amnion; Epithelial cell; Delivery; Neutrophil
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.103.016204

Intra-amniotic secretion and abundance of epithelial cell-derived neutrophil-activating peptide (ENA)-78, a potent chemoattractant
and activator of neutrophils, was studied in the context of term and preterm parturition. Staining of ENA-78 immunoperoxidase
was localized predominantly to chorionic trophoblasts and amniotic epithelium in term and preterm gestational membranes, with
weaker and less consistent staining in decidual cells. The abundance of ENA-78 in membrane tissue homogenates was significantly
increased (∼4-fold) with term labor in amnion (n = 15), and with preterm labor (∼30-fold) in amnion and choriodecidua (n =
31). In amnion tissue homogenate extracts, ENA-78 levels were positively correlated with the degree of leukocyte infiltration
( r 2 = 0.481). In amniotic fluids, median ENA-78 levels from pregnancies with preterm labor without intra-amniotic infection were
significantly lower ( P < 0.01 by ANOVA) than those from pregnancies with preterm deliveries with infection; levels in samples derived from term
pregnancies were similar before and after labor. Production of ENA-78 by amnion monolayers was stimulated in a concentration-dependent
fashion by both interleukin-1β and tumor necrosis factor α. Production of ENA-78 by choriodecidual explants was increased
modestly after 2–4 h of exposure to lipopolysaccharide (5 μg/ml). An immunoreactive doublet (∼8 kDa) was detected in choriodecidual
explant-conditioned media by immunoblotting. We conclude that ENA-78, derived from the gestational membranes, is present in
increased abundance in the amniotic cavity in response to intrauterine infection and, hence, may play a role in the mechanism
of infection-driven preterm birth and rupture of membranes secondary to leukocyte recruitment and activation.