Gomez-Lopez Nardhy, Romero Roberto, Xu Yi, Garcia-Flores Valeria, Leng Yaozhu, Panaitescu Bogdan, Miller Derek, Abrahams Vikki M, Hassan Sonia S
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA.
Am J Reprod Immunol. 2017 May;77(5). doi: 10.1111/aji.12648. Epub 2017 Feb 24.
Inflammasome activation requires two steps: priming and assembly of the multimeric complex. The second step includes assembly of the sensor molecule and adaptor protein ASC (an apoptosis-associated speck-like protein containing a CARD), which results in ASC speck formation and the recruitment of caspase (CASP)-1. Herein, we investigated whether there is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes from women who underwent spontaneous labor at term.
Using in situ proximity ligation assays, ASC/CASP-1 complexes were determined in the chorioamniotic membranes from women who delivered at term without labor or underwent spontaneous labor at term with or without acute histologic chorioamnionitis (n=10-11 each). Also, ASC speck formation was determined by flow cytometry in the choriodecidual leukocytes isolated from women who delivered at term with or without spontaneous labor (n=9-12 each).
(i) ASC/CASP-1 complexes were detected in the chorioamniotic membranes; (ii) ASC/CASP-1 complexes were greater in the chorioamniotic membranes from women who underwent spontaneous labor at term than in those without labor; (iii) ASC/CASP-1 complexes were even more abundant in the chorioamniotic membranes from women who underwent spontaneous labor at term with acute histologic chorioamnionitis than in those without this placental lesion; (iv) ASC speck formation was detected in the choriodecidual leukocytes; and (v) ASC speck formation was greater in the choriodecidual leukocytes isolated from women who underwent spontaneous labor at term than in those without labor.
There is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes during spontaneous labor at term.
炎性小体激活需要两个步骤:启动和多聚体复合物的组装。第二步包括传感器分子和接头蛋白ASC(一种含有CARD的凋亡相关斑点样蛋白)的组装,这会导致ASC斑点形成并募集半胱天冬酶(CASP)-1。在此,我们研究了足月自然分娩女性的羊膜绒毛膜和绒毛蜕膜白细胞中是否存在炎性小体组装。
使用原位邻近连接分析法,在足月未分娩或足月自然分娩且伴有或不伴有急性组织学绒毛膜羊膜炎的女性(每组n = 10 - 11)的羊膜绒毛膜中测定ASC/CASP-1复合物。此外,通过流式细胞术在足月分娩且伴有或不伴有自然分娩的女性(每组n = 9 - 12)分离的绒毛蜕膜白细胞中测定ASC斑点形成。
(i)在羊膜绒毛膜中检测到ASC/CASP-1复合物;(ii)足月自然分娩女性的羊膜绒毛膜中的ASC/CASP-1复合物比未分娩女性的更多;(iii)足月自然分娩且伴有急性组织学绒毛膜羊膜炎的女性的羊膜绒毛膜中的ASC/CASP-1复合物比无此胎盘病变的女性更为丰富;(iv)在绒毛蜕膜白细胞中检测到ASC斑点形成;(v)足月自然分娩女性分离的绒毛蜕膜白细胞中的ASC斑点形成比未分娩女性的更多。
足月自然分娩期间,羊膜绒毛膜和绒毛蜕膜白细胞中存在炎性小体组装。