The Expression And Roles Of Chemokines And Their Receptors At The Materno-fetal Interface

Chemokines are a group of small molecules (8-14kd) cytokines, which are classified into four subfamilies. The various chemokines interact with a subset of seven transmembrane G protein-coupled receptors termed chemokine receptors. Chemokines were initially recognized to play a role in leukocyte migration, both in physiological and pathological contexts. These molecules control immuno-competent cell trafficking and recirculation across the blood vessels, lymph, lymphoid organs and tissues, an important process in host immune surveillance, and in acute and chronic inflammatory responses, and so on. Since CXCR4 and CCR5 were discovered as co-receptors required for HIV-1 infection into permissive cells in 1996, much attention has been paid to chemokines and their receptors. Now it is well known that chemokines and their receptors not only play fundamental roles in body development, homeostasis, and immune system function, but also are important in the angiogenesis and angiostatic processes, tumor genesis and metastasis. Chemokines and their receptors have been implicated as pivotal players in many physiological and pathological situations, but little is known about their expression and function at the materno-fetal interface. The mechanisms by which human hemiallogeneic placenta avoids rejection by the maternal immune system are under intense investigation, and it has now become clear that decidual lymphocytes have unique functions in local cytokine production, promoting endovascular invasion and placental development so as to keep pregnancy going smoothly. More than 70% of decidual lymphocytes are NK cells characterized by CD56brightCD16? phenotype. The enrichment of the decidua with this specific NK subset is outstanding compared to the 10% composition of NK cells in the peripheral blood, where the CD56brightCD16? population composes only 10-15% out of the total peripheral NK population. The reasons and the mechanisms controlling the accumulation of the CD56brightCD16?NK cells in the decidua are still almost unknown. Since chemokines and their receptors are key players in leukocytes communication and migration, it is very reasonable to speculate that chemokine receptors and their ligands are involved in the preferential accumulation of the CD56brightCD16? NK cells in the decidua: the chemokines at the materno-fetal interface act with the chemokine receptors expressed on CD56brightCD16?NK cells, then attract CD56brightCD16?NK cell to accumlate in the decidua.Although chemokine receptors are predominantly expressed by hematopoietic cells, certain types are also expressed by endothelial cells, epithelial cells and neural cells. The chemokines and their receptors could regulate cell proliferation and differentiation. Recently, a study showed that exogenous chemokines up-regulated proliferation and hCG production of choriocarcinoma cell lines, so it is interesting to speculate that chemokines at the materno-fetal interface may interact with chemokine receptors expressed on trophoblast cells so as to regulate thir growth, differentiation and function in paracrine or autocrine manners. In addition, the expression of chemokine receptors by placenta, especially trophoblast cells, may also provide some useful insights into the cellular mechanisms of trans-placental HIV-1 infection and the prevention of vertical intrauterine transmission. In the present study the main research focuses are as follows:1.Isolation, purification and primary culture of the villous cytotrophoblasts (VCT) and extravillous cytotrophoblasts (EVCT) from human first trimester chorionic villi. When cytotrophoblast cells were selectively released under different tissue digestion conditions, two types of trophoblast cells could be easily isolated. Immunocytochemistry and electron microscopy revealed the biological characteristics of these cells. The results showed EVCT could be isolated with gentle enzymatic digestion while VCT isolation required more intense disaggregation conditions. EVCT cultured on Matrigel exhibited positive staining fo...