Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA.
Biol Reprod. 2011 Sep;85(3):626-34. doi: 10.1095/biolreprod.111.092494. Epub 2011 May 18.
The a2 isoform of vacuolar ATPase (ATP6V0A2 referred to as a2V) plays a pivotal role in successful pregnancy and provides a microenvironment to maintain the delicate immunological balance at the feto-maternal interaction. We studied the expression of a2V mRNA in embryos and placenta of abortion-prone (female CBA × male DBA) murine matings or LPS (lipopolysaccharide)-treated mice. The expression of a2V was significantly higher in the placentas of nonabortion-prone (female BALB/c × male BALB/c and female CBA × male BALB/c) matings compared with the abortion-prone (female CBA × male DBA) mating. The expression of a2V was significantly decreased in the placentas treated with LPS in both female CBA × male DBA and female BALB/c × male BALB/c mating combinations with increased Lif, Il1b, and Tnf expression in the placenta. Decreased expression of a2V in the placenta is directly correlated with high percentages of pregnancy loss in abortion-prone mating (female CBA × male DBA) as well as in LPS-treated animals. The normal expression of placental a2V on Day 16 in the nonabortion-prone matings correlated with higher Mcp1 (monocyte chemotactic protein 1) gene expression, markedly higher infiltration of M1 and M2 macrophages, and no significant polarization patterns (M1/M2 = 1.2-1.6). However, in the abortion-prone mating, decreased placental a2V expression correlated with significantly lower Mcp1 gene expression with less infiltration of M1 and M2 macrophages and with polarization patterns skewed to M1 phenotypes (M1/M2 = 3.9-4.2). These data indicate that the higher expression of placental a2V is associated with dynamic infiltration of M1 and M2 macrophages through the induction of Mcp1 expression. This strengthens our hypothesis that a2V regulates the delicate cytokine and chemokine networks that coordinate the recruitment of macrophages for successful placental development and growth at the feto-maternal interface.
空泡型质子泵（ATP6V0A2，简称 a2V）的 a2 同工型在成功妊娠中起着关键作用，并为滋养层-母体相互作用提供了维持微妙免疫平衡的微环境。我们研究了流产易感（CBA 雌性×DBA 雄性）交配或 LPS（脂多糖）处理的小鼠胚胎和胎盘中 a2V mRNA 的表达。与流产易感（CBA 雌性×DBA 雄性）交配相比，非流产易感（BALB/c 雌性×BALB/c 雄性和 CBA 雌性×BALB/c 雄性）交配的胎盘 a2V 表达显著更高。在 CBA 雌性×DBA 雄性和 BALB/c 雌性×BALB/c 雄性交配组合中，LPS 处理的胎盘中 a2V 的表达显著降低，同时胎盘 Lif、Il1b 和 Tnf 的表达增加。胎盘 a2V 表达降低与流产易感（CBA 雌性×DBA 雄性）交配和 LPS 处理动物中的高妊娠丢失百分比直接相关。非流产易感交配（CBA 雌性×BALB/c 雄性）中第 16 天胎盘 a2V 的正常表达与更高的单核细胞趋化蛋白 1（Mcp1）基因表达相关，显著更高的 M1 和 M2 巨噬细胞浸润，以及没有明显的极化模式（M1/M2=1.2-1.6）。然而，在流产易感交配中，胎盘 a2V 表达降低与 Mcp1 基因表达显著降低相关，M1 和 M2 巨噬细胞浸润减少，极化模式偏向 M1 表型（M1/M2=3.9-4.2）。这些数据表明，胎盘 a2V 的高表达与通过诱导 Mcp1 表达而动态浸润 M1 和 M2 巨噬细胞有关。这进一步证实了我们的假设，即 a2V 调节微妙的细胞因子和趋化因子网络，协调巨噬细胞募集，以促进胎盘在胎-母界面的成功发育和生长。
