Fractalkine (CX3CL1) and its CX3C chemokine receptor 1 (CX3CR1) in the human placenta and amnion under physiologic and pathologic conditions.

摘要

Cytokines, including chemokines (chemotactic cytokines) mediating inflammatory and effector functions in the human utero-feto-placental unit forms a specific network. Our investigations of this network started in the early 1990s in the Laboratory of Placental Research of the Medical University of Warsaw, Poland. Discovered in 1997, chemokine CX3CL1 (fractalkine, neurotactin) is the sole member of the CX3C class chemokines. CX3CL1 reveals both adhesive and chemotactic properties that makes it unique among the chemokines. This overview, based on author's own scientific experience and the results of others, considers the role of CX3CL1 in physiologic and complicated human pregnancy. The studies were focused on the relationship between spontaneous and lipopolysaccharide (LPS)-induced CX3CL1 production and its own receptor CX3CR1 local expression in the uterus, placenta and fetal membranes. Most of them were conducted in vitro, using cultures of isolated trophoblast cells and human amniotic epithelial cells (HAEC). Analyses of hypoxia influence and CX3CR1 blockade were included in the experimental projects. Studies revealed that endometrially derived CX3CL1 may be crucial for the attachment and invasion of the fetal trophoblast cells during implantation. Pathophysiology of the trophoblast in intrauterine growth retardation (IUGR) included significant reduction of both CX3CL1 synthesis and CX3CR1 expression. Hypoxia reduced production of CX3CL1 in trophoblast and HAEC cultures. However, in some inflammatory conditions (placentitis, chorioamnionitis) this effect was less evident, compared to the normal trophoblast or HAEC, respectively. Such a resistance to hypoxia was related with overexpression of the CX3CR1. In all experiments CX3CR1 blockade reduced or cancelled response to LPS. Future possibilities of the implementation of these results into clinical obstetric and gynecologic practice are discussed.