RESUMEN
Background: Inflammation is a condition that jeopardizes the continuity of pregnancy because it increases the secretion of chemokines that favor the migration of leukocytes from maternal and fetal circulations to the cervix, placenta, and the chorioamniotic membranes. During pregnancy, the level of prolactin (PRL) in the amniotic fluid is high; there is evidence to suggest that PRL contributes to maintain a privileged immune environment in the amniotic cavity. We test the effect of prolactin on the secretion profile of chemokines in human fetal membranes.Methods: Nine fetal membranes collected from healthy nonlabouring cesarean deliveries at term. We placed whole membrane explants in a two-chamber culture system. Choriodecidua and amniotic chambers were pretreated with 250, 500, 1000, or 4000 ng/ml of PRL for 24 h, then choriodecidua was cotreated with 500 ng/ml of lipopolysaccharide (LPS) and PRL for 24 h. We used ELISA to measure secreted levels of four chemokines (RANTES, monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and IL-8) in both amnion and choriodecidua regions.Results: In comparison with basal conditions, LPS treatment induced significantly higher secretion of RANTES, MCP-1, and MIP-1α, but not of IL-8. RANTES was mainly produced by choriodecidua and cotreatment with PRL significantly decreased its LPS-induced secretion. MCP-1 was primarily produced by the amnion and its secretion was only inhibited by 4000 ng/ml of PRL. Both membrane regions produced MIP-1α, which was significantly inhibited at 1000 and 4000 ng/ml PRL concentrations. IL-8 showed no significant changes regardless of PRL concentration.Conclusion: PRL inhibits the differential secretion of proinflammatory chemokines by human fetal membranes.
Asunto(s)
Membranas Extraembrionarias , Lipopolisacáridos , Prolactina , Amnios , Quimiocinas , Femenino , Humanos , Embarazo , Prolactina/fisiologíaRESUMEN
One of the characteristics of the labor process in women is leukocyte recruitment into reproductive tissues. These migrating cells may play a role in the induction of functional and biochemical changes associated with the rupture of fetal membranes during labor. This study was undertaken to assess whether human fetal membranes induce leukocyte chemotaxis during labor as well as to identify and characterize leukocyte chemoattractants secreted by these tissues. Leukocyte chemotactic activity of fetal membrane extracts obtained from women with full-term pregnancies and spontaneous active labor was compared with extracts from women without labor. The number and phenotype of attracted leukocytes were analyzed by flow cytometry. Chemokines were quantified using a Multiplex system and were identified by immunofluorescence histochemistry. Although all tested extracts induced chemotaxis of leukocytes, those prepared from women undergoing labor induced higher responses. Polymorphonuclear leukocyte chemotaxis increased approximately three-fold in response to extract from fetal membranes with labor. The same extracts elicited a significant increase in attracted monocytes (36-fold) as well as T and B lymphocytes, and NK cells (all five-fold) when compared to extracts from women without labor. This enhanced chemotactic activity was associated with the presence of IL-8, MCP-1, IP-10 and MIP-1alpha. We conclude that fetal membrane extracts obtained from women during labor exhibit selective chemotaxis for specific leukocyte subpopulations in vitro. This process may contribute to a microenvironment composed of specific leukocytes that promotes and amplifies biochemical changes in the fetal membranes during labor.