Gaffuri B, Vigano P, Nozza A, Gornati G, Di Blasio A M, Vignali M
Department of Obstetrics and Gynecology II, University of Milano, Italy.
Biol Reprod. 1998 Apr;58(4):1003-8. doi: 10.1095/biolreprod58.4.1003.
Intercellular adhesion molecule-1 (ICAM-1) is a ligand for the integrins lymphocyte function-associated antigen-1 (LFA-1) and complement receptor-3 (Mac-1), making it an important participant in many immune and inflammatory processes. Previous studies suggested that lack or reduced expression of ICAM-1 on trophoblast might partially explain its resistance to lysis by cytotoxic effectors. However, whether or not the adhesion molecule is expressed on placental cells is still a matter of debate. In this study, we determined ICAM-1 expression at mRNA, surface, and soluble protein levels on human trophoblasts throughout their functional differentiation in culture from cytotrophoblasts into syncytiotrophoblasts. Placental cells were obtained from 6 term placentas derived from normal pregnancies. ICAM-1 mRNA was detected by reverse transcription-polymerase chain reaction using two oligonucleotide primers specific for the human ICAM-1 gene. A single major DNA band of the expected size (943 base pairs) was obtained in both cytotrophoblasts and syncytiotrophoblasts. Flow cytometric analysis demonstrated expression of surface ICAM-1 protein on 45.5+/-3.5% of cytotrophoblasts. No changes were observed during differentiation in culture. Levels of the soluble form of ICAM-1 (sICAM-1) released by placental cells were undetectable when assessed by a specific ELISA. Finally, we investigated the effect of pro-inflammatory cytokines on placental ICAM-1 expression. Treatment of cultured trophoblasts for 24 h with interleukin-1beta (1 ng/ml) or tumor necrosis factor alpha (1 ng/ml) increased surface expression of ICAM-1 without inducing sICAM-1 shedding. However, on placental cells, the two cytokines exerted stimulatory effects lower than those detected on endometrial cells used as positive control. These observations document that the ICAM-1 gene is expressed in both cytotrophoblasts and syncytiotrophoblasts, suggesting that the molecule may be of value for some immune-mediated processes. On the other hand, the low sensitivity of trophoblasts to cytokine-mediated induction of ICAM-1 expression might represent a functional mechanism contributing to maternal tolerance for fetal graft.
细胞间黏附分子-1（ICAM-1）是整合素淋巴细胞功能相关抗原-1（LFA-1）和补体受体-3（Mac-1）的配体，使其成为许多免疫和炎症过程的重要参与者。先前的研究表明，滋养层细胞上ICAM-1的缺乏或表达减少可能部分解释了其对细胞毒性效应物裂解的抗性。然而，这种黏附分子是否在胎盘细胞上表达仍存在争议。在本研究中，我们在体外培养的人滋养层细胞从细胞滋养层细胞分化为合体滋养层细胞的整个功能分化过程中，测定了ICAM-1在mRNA、表面和可溶性蛋白水平的表达。胎盘细胞取自6例正常妊娠足月胎盘。使用针对人ICAM-1基因的两个寡核苷酸引物，通过逆转录-聚合酶链反应检测ICAM-1 mRNA。在细胞滋养层细胞和合体滋养层细胞中均获得了预期大小（943个碱基对）的单一主要DNA条带。流式细胞术分析显示，45.5±3.5%的细胞滋养层细胞表面表达ICAM-1蛋白。在培养分化过程中未观察到变化。通过特异性酶联免疫吸附测定法评估时，未检测到胎盘细胞释放的可溶性ICAM-1（sICAM-1）水平。最后，我们研究了促炎细胞因子对胎盘ICAM-1表达的影响。用白细胞介素-1β（1 ng/ml）或肿瘤坏死因子α（1 ng/ml）处理培养的滋养层细胞24小时，可增加ICAM-1的表面表达，且不诱导sICAM-1脱落。然而，在胎盘细胞上，这两种细胞因子的刺激作用低于用作阳性对照的子宫内膜细胞。这些观察结果表明，ICAM-1基因在细胞滋养层细胞和合体滋养层细胞中均有表达，提示该分子可能在某些免疫介导过程中具有重要作用。另一方面，滋养层细胞对细胞因子介导的ICAM-1表达诱导的低敏感性可能是母体对胎儿移植物产生耐受性的一种功能机制。
