Gharanei Seley, Fishwick Katherine, Peter Durairaj Ruban, Jin Tianrong, Siamantouras Eleftherios, Liu Kuo-Kang, Straube Anne, Lucas Emma S, Weston Christopher J, Rantakari Pia, Salmi Marko, Jalkanen Sirpa, Brosens Jan J, Tan Bee Kang
Warwick Medical School, University of Warwick, Coventry, United Kingdom.
Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry, United Kingdom.
Front Cell Dev Biol. 2021 Jan 18;8:621016. doi: 10.3389/fcell.2020.621016. eCollection 2020.
Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule and a primary amine oxidase involved in immune cell trafficking. Leukocyte extravasation into tissues is mediated by adhesion molecules expressed on endothelial cells and pericytes. Pericytes play a major role in the angiogenesis and vascularization of cycling endometrium. However, the functional properties of pericytes in the human endometrium are not known. Here we show that pericytes surrounding the spiral arterioles in midluteal human endometrium constitutively express VAP-1. We first characterize these pericytes and demonstrate that knockdown of VAP-1 perturbed their biophysical properties and compromised their contractile, migratory, adhesive and clonogenic capacities. Furthermore, we show that loss of VAP-1 disrupts pericyte-uterine natural killer cell interactions . Taken together, the data not only reveal that endometrial pericytes represent a cell population with distinct biophysical and functional properties but also suggest a pivotal role for VAP-1 in regulating the recruitment of innate immune cells in human endometrium. We posit that VAP-1 could serve as a potential biomarker for pregnancy pathologies caused by a compromised perivascular environment prior to conception.
血管黏附蛋白-1(VAP-1)是一种炎症诱导性黏附分子,也是一种参与免疫细胞运输的伯胺氧化酶。白细胞渗入组织是由内皮细胞和周细胞上表达的黏附分子介导的。周细胞在周期性子宫内膜的血管生成和血管化过程中起主要作用。然而,人类子宫内膜中周细胞的功能特性尚不清楚。在此,我们表明,在人类子宫内膜黄体中期,螺旋小动脉周围的周细胞组成性表达VAP-1。我们首先对这些周细胞进行了表征,并证明VAP-1的敲低扰乱了它们的生物物理特性,并损害了它们的收缩、迁移、黏附和克隆能力。此外,我们表明VAP-1的缺失破坏了周细胞与子宫自然杀伤细胞的相互作用。综上所述,这些数据不仅揭示了子宫内膜周细胞代表了具有独特生物物理和功能特性的细胞群体,而且还表明VAP-1在调节人类子宫内膜中固有免疫细胞的募集中起关键作用。我们推测,VAP-1可能作为受孕前血管周围环境受损所致妊娠病理的潜在生物标志物。