Chemokine Scavenger D6 Is Expressed by Trophoblasts and Aids the Survival of Mouse Embryos Transferred into Allogeneic Recipients

Madigan, J. et al. (2010) Chemokine Scavenger D6 Is Expressed by Trophoblasts and Aids the Survival of Mouse Embryos Transferred into Allogeneic Recipients. Journal of Immunology, 184(6), pp. 3202-3212. (doi:10.4049/jimmunol.0902118)

Madigan, J. et al. (2010) Chemokine Scavenger D6 Is Expressed by Trophoblasts and Aids the Survival of Mouse Embryos Transferred into Allogeneic Recipients. Journal of Immunology, 184(6), pp. 3202-3212. (doi:10.4049/jimmunol.0902118)

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Abstract

Proinflammatory CC chemokines are thought to drive recruitment of maternal leukocytes into gestational tissues and regulate extravillous trophoblast migration. The atypical chemokine receptor D6 binds many of these chemokines and is highly expressed by the human placenta. D6 is thought to act as a chemokine scavenger because, when ectopically expressed in cell lines in vitro, it efficiently internalizes proinflammatory CC chemokines and targets them for destruction in the absence of detectable chemokine-induced signaling. Moreover, D6 suppresses inflammation in many mouse tissues, and notably, D6-deficient fetuses in D6-deficient female mice show increased susceptibility to inflammation-driven resorption. In this paper, we report strong anti-D6 immunoreactivity, with specific intracellular distribution patterns, in trophoblast-derived cells in human placenta, decidua, and gestational membranes throughout pregnancy and in trophoblast disease states of hydatidiform mole and choriocarcinoma. We show, for the first time, that endogenous D6 in a human choriocarcinoma-derived cell line can mediate progressive chemokine scavenging and that the D6 ligand CCL2 can specifically associate with human syncytiotrophoblasts in term placenta in situ. Moreover, despite strong chemokine production by gestational tissues, levels of D6-binding chemokines in maternal plasma decrease during pregnancy, even in women with pre-eclampsia, a disease associated with increased maternal inflammation. In mice, D6 is not required for syngeneic or semiallogeneic fetal survival in unchallenged mice, but interestingly, it does suppress fetal resorption after embryo transfer into fully allogeneic recipients. These data support the view that trophoblast D6 scavenges maternal chemokines at the fetomaternal interface and that, in some circumstances, this can help to ensure fetal survival. The Journal of Immunology, 2010,184: 3202-3212

Item Type:Articles
Keywords:BLOOD CARE CELLS DECOY RECEPTOR D6 DISEASE growth haemostasis Human HUMAN PLACENTA IMMUNE immunity inflammation LEVEL LIGAND MONOCYTES NATURAL-KILLER-CELLS PLASMA PREGNANCY RECIPIENTS Scotland SEQUESTRATION SURFACE SURVIVAL SUSCEPTIBILITY WOMEN
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Menzies, Dr Fiona and Nelson, Professor Scott and Freeman, Dr Dilys and Young, Mrs Anne and Madigan, Dr Judith and Nibbs, Professor Robert and Greer, Prof Ian and Graham, Professor Gerard
Authors: Madigan, J., Freeman, D. J., Menzies, F., Forrow, S., Nelson, S. M., Young, A., Sharkey, A., Moffet, A., Graham, G. J., Greer, I. A., Rot, A., and Nibbs, R. J. B.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
ISSN:0022-1767

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