The Role of Chemokines in Term and Premature Rupture of the Fetal Membranes: A Review1 (original) (raw)

Fetal membranes exhibit selective leukocyte chemotaxic activity during human labor

Journal of Reproductive Immunology, 2009

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-1␣. 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.

Choriodecidua and amnion exhibit selective leukocyte chemotaxis during term human labor

American Journal of Obstetrics and Gynecology, 2011

The purpose of this study was to compare the chemotactic activity of the choriodecidua and amnion, and to identify the phenotype of the leukocytes chemoattracted by each tissue. STUDY DESIGN: Amnion, choriodecidua and whole fetal membranes extracts were obtained from women at term (Ͼ37 weeks of gestation) with or without labor (n ϭ 5 each). Extracts were assayed for leukocyte chemotactic activity, and the number and phenotype of the chemoattracted leukocytes were characterized by flow cytometry. RESULTS: Although all of the extracts exhibited chemotactic activity, more leukocytes were chemoattracted by the choriodecidua and the whole fetal membranes during labor compared with no labor (P ϭ .010, .008). During labor the choriodecidua is responsible for granulocyte, Tlymphocyte, monocyte, and natural killer-cell chemoattraction, and the amnion is responsible for B-lymphocyte chemoattraction. CONCLUSION: Choriodecidua and amnion exhibit chemotactic activity for selective leukocytes and thus, each fetal membrane differentially regulates leukocyte chemotactic activity during labor.

Decidual Inflammation Drives Chemokine-Mediated Immune Infiltration Contributing to Term Labor

The Journal of Immunology, 2021

Infiltration of maternal peripheral leukocytes into the uterine tissues is a critical event occurring prior to, during and after term labor (TL). Here we investigate the contribution of uterine smooth muscle (myometrium) and pregnant endometrium (decidua) to the inflammatory process during human TL. We hypothesize that labor-related physiological inflammation is orchestrated by uterine-secreted cytokines, which dually activate the uterine vascular endothelium and maternal leukocytes to promote their adhesion and infiltration into the uterus. Using Luminex and ELISA assays we examine a full range of cytokines (45 proteins) in media conditioned by primary decidual and myometrial cells from TL and term not in labor (TNL) women. The effect of conditioned media on the activation of human uterine microvascular endothelial cells (UtMVEC) was measured by qPCR, and on peripheral leukocytes, by flow cytometry. Transendothelial migration of calcein-labeled primary leukocytes towards media was assessed by fluorometry. Stromal decidual cells secrete significantly higher levels of multiple cytokines compared to myometrial cells (P<0.05), and significantly more cytokines during TL than TNL. These cytokines activate UtMVEC through the upregulation of cell adhesion molecule VCAM-1, and peripheral leukocytes-by upregulation of CD11b. Furthermore, multiple cytokines secreted from the TL decidua and myometrium significantly increase migration of granulocytes, monocytes, and lymphocytes compared to TNL (P<0.05), which was blocked by a Broad Spectrum Chemokine Inhibitor (FX125L). These data reveal the critical role for decidual-and myometrial-secreted

1141478634 Amniochorion secretes chemotactic signals for leukocytes during human labor

American Journal of Reproductive Immunology, 2006

Objective: Leukocytes arriving to choriodecidua during labor are capable to secrete cytokines and collagenases that may play a role in extracellular matrix degradation leading to the rupture of amniochorion. The aim of this work was to study the role of amniochorion in the active recruitment of leukocytes through production of specific chemokynes during labor. Methods: Amniochorion explants were obtained from women at term with spontaneous labor (n = 4) and subjected to cesarean section without labor (n = 4). Explant cultures were carried out during 24 hr and an homogenate including the culture media was made after this period. Cell free extracts were tested in Boyden chambers for chemotaxis using leukocytes from maternal blood obtained from women with (n = 2) and without labor (n = 2). Attracted cells were analyzed by flow cytometry for count and immunophenotype. Chemokynes were identified in the extracts using a commercial chemiarray. Results: All tested amniochorion extracts induced chemotaxis for leukocytes; however, those from labor tissues induced a higher chemotactic activity than the correspondent non-in-labor tissues (P = 0.003). Chemotactic effect was higher over leukocytes from labor women (P = 0.001). More than 80% of the attracted cells were polymorphonuclears in all cases. IL-8 was the main chemokyne found in all extracts; however its concentration was increased in extracts from labor. Conclusions: Fetal membranes induced chemotaxis for leukocytes and this condition is enhanced by the presence of labor. Amniochorion under active labor secretes IL-8 which induces a preferential chemotaxis for polymorphonuclears. Infiltration of these cells in choriodecidua during labor may play a role in the amniochorion degradation associated to rupture.

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

Genes and immunity, 2018

Prior to and during the process of human labor, maternal circulating leukocytes infiltrate the maternal-fetal interface (choriodecidua) and become activated resembling choriodecidual leukocytes. Since, there is no evidence comparing maternal circulating and choriodecidual leukocytes, herein, we characterized their transcriptome and explored the biological processes enriched in choriodecidual leukocytes. From women undergoing spontaneous term labor we isolated circulating and choriodecidual leukocytes, performed microarray analysis (n = 5) and qRT-PCR validation (n = 9) and interaction network analysis with up-regulated genes. We found 270 genes up-regulated and only 17 genes down-regulated in choriodecidual leukocytes compared to maternal circulating leukocytes. The most up-regulated genes were CCL18, GPNMB, SEPP1, FN1, RNASE1, SPP1, C1QC, and PLTP. The biological processes enriched in choriodecidual leukocytes were cell migration and regulation of immune response, chemotaxis, and h...