engleski

Chemokine Decoy receptor D6 acts as a chemokine scavenger at the maternal-fetal interface

PROBLEM: D6 is a 7-transmembrane-domain receptor that, in contrast to other chemokine receptors, does not seem to signal after ligand engagement. It binds most inflammatory, but not homeostatic, CC chemokines and shuttles in a ligand-independent way from the plasma membrane to endocytic compartments where chemokines are targeted for degradation. It is expressed on endothelial cells of lymphatic afferent vessels in skin, gut and lung, where it acts as a gatekeeper for inflammatory chemokines transfer to lymph nodes, thereby limiting leukocyte infiltration and concomitant inflammation. D6 is expressed at high levels in placenta, but its cellular location and function in this tissue are unknown. METHODS: D6 expression in placenta tissue was detected by immunohistochemistry. Its expression in choriocarcinoma cell lines (BeWo, Jar and Jeg-3) was detected by RT-PCR and confocal microscopy. ELISA assay was used for scavenging and transcytosis experiments. RESULTS: In placenta, D6 expression was evident in syncytiotrophoblast. Consistently with this, choriocarcinoma cell lines Jar, Jeg-3 (invading trophoblast) and BeWo (syncytiotrophoblast) expressed D6 mRNA and protein. In all three cell lines D6 ligands were efficiently scavenged in comparison with CHO/D6 transfectants. In polarised BeWo cells D6 was expressed in the apical compartement. There was no evidence for D6 mediated chemokine transfer through the BeWo monolayer. CONCLUSIONS: D6 is expressed on syncytiotrophoblast cells in placenta and in choriocarcinoma cell lines where it acts as a scavenger receptor and does not support chemokine transcytosis. Thus, D6 is a peculiar chemokine receptor strategically located to tune inflammation at the maternal-fetal interface by means of chemokine scavenging.

Decoy receptor D6; placenta

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