Dong H, Burke S D, Croy B A
Department of Anatomy and Cell Biology, Queen's University, Kingston, ON K7L 3N6, Canada.
Placenta. 2008 Feb;29(2):201-9. doi: 10.1016/j.placenta.2007.10.003. Epub 2007 Nov 26.
Distinctive patterns of vascular cell adhesion molecule expression in early mouse decidua establish niches that recruit different subtypes of immune cells. In normal gestation day (gd)8 decidua, vascular cell adhesion molecule (VCAM)-1 and mucosal addressin cell adhesion molecule (MAdCAM)-1 occur in different regions enriched by uterine Natural Killer (uNK) cells and monocytes, respectively. UNK cells prepare endometrial spiral arteries for pregnancy-induced structural modifications, a process deficient in decidua of type 1 diabetic mice and women. In non-obese diabetic (NOD) mice, onset of insulitis coincides with islet expression of VCAM-1, MAdCAM-1 and peripheral lymph node addressin (PNAd), a molecule implicated in extravasation of human uNK precursor cells. We used immunohistochemistry to address the combined effects of diabetes and pregnancy on gd6 and 8 pancreatic and decidual expression of VCAM-1, MAdCAM-1 and PNAd and assessed the effect of diabetes on early uNK cell numbers. Normoglycemic (n) and diabetic (d) NOD and C57Bl/6 (B6) mice were studied. Pregnancy increased addressin expression in the pancreata of all mice with n- and d-NOD pancreata having stronger endothelial expression of VCAM-1, MAdCAM-1 and PNAd than B6. VCAM-1 expression was localized to uterine endothelium, including that of spiral arteries and was lower in d- than in n-NOD or B6 mice. MAdCAM-1 was localized to uterine endothelium and was lower in n- and d-NOD than in B6. PNAd expression was only observed in uterine epithelium and was stronger in d- than in n-NOD or B6. In all groups, only VCAM-1 had stronger expression in decidua than in pancreas. A mild elevation in uNK cells was present in n-and d-NOD mice at gd6 but not at gd8 when a higher proliferation index was found compared with B6. Thus, in type 1 diabetic gestations in mice, signals for the recruitment of circulating cells are reduced in uterus and elevated in pancreas.
小鼠早期蜕膜中血管细胞黏附分子的独特表达模式形成了招募不同亚型免疫细胞的微环境。在正常妊娠第8天（gd8）的蜕膜中，血管细胞黏附分子（VCAM）-1和黏膜地址素细胞黏附分子（MAdCAM）-1分别出现在富含子宫自然杀伤（uNK）细胞和单核细胞的不同区域。uNK细胞为妊娠诱导的结构改变准备子宫内膜螺旋动脉，这一过程在1型糖尿病小鼠和女性的蜕膜中缺乏。在非肥胖糖尿病（NOD）小鼠中，胰岛炎的发作与胰岛中VCAM-1、MAdCAM-1和外周淋巴结地址素（PNAd）的表达同时出现，PNAd是一种与人类uNK前体细胞外渗有关的分子。我们使用免疫组织化学来研究糖尿病和妊娠对gd6和8时胰腺和蜕膜中VCAM-1、MAdCAM-1和PNAd表达的联合影响，并评估糖尿病对早期uNK细胞数量的影响。研究了血糖正常（n）和糖尿病（d）的NOD和C57Bl/6（B6）小鼠。妊娠增加了所有小鼠胰腺中地址素的表达，n-NOD和d-NOD胰腺中VCAM-1、MAdCAM-1和PNAd的内皮表达比B6更强。VCAM-1表达定位于子宫内皮，包括螺旋动脉的内皮，d-NOD小鼠中的表达低于n-NOD或B6小鼠。MAdCAM-1定位于子宫内皮，n-NOD和d-NOD中的表达低于B6。PNAd表达仅在子宫上皮中观察到，d-NOD中的表达比n-NOD或B6更强。在所有组中，只有VCAM-1在蜕膜中的表达比在胰腺中更强。在gd6时，n-NOD和d-NOD小鼠中的uNK细胞有轻度升高，但在gd8时没有，此时与B6相比发现增殖指数更高。因此，在小鼠1型糖尿病妊娠中，子宫中循环细胞招募信号减少，胰腺中信号升高。
