EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1 MESSENGER-RIBONUCLEIC-ACID AND PROTEIN IN HUMAN TERM PLACENTAL CELLS AND ITS MODULATION BY PRO-INFLAMMATORY CYTOKINES (INTERLEUKIN-1-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA)

Intercellular adhesion molecule-1 (ICAM-1) is a ligand for the integri ns lymphocyte function-associated antigen-1 (LFA-1) and complement rec eptor-3 (Mac-1), making it an important participant in many immune and inflammatory processes. Previous studies suggested that lack or reduc ed expression of ICAM-1 on trophoblast might partially explain its res istance to lysis by cytotoxic effecters. However, whether or not the a dhesion molecule is expressed on placental cells is still a matter of debate. In this study, we determined ICAM-1 expression at mRNA, surfac e, and soluble protein levels on human trophoblasts throughout their f unctional differentiation in culture from cytotrophoblasts into syncyt iotrophoblasts. Placental cells were obtained from 6 term placentas de rived from normal pregnancies. ICAM-1 mRNA was detected by reverse tra nscription-polymerase chain reaction using two oligonucleotide primers specific for the human ICAM-1 gene. A single major DNA band of the ex pected size (943 base pairs) was obtained in both cytotrophoblasts and syncytiotrophoblasts. Flow cytometric analysis demonstrated expressio n of surface ICAM-1 protein on 45.5 +/- 3.5% of cytotrophoblasts. No c hanges were observed during differentiation in culture. Levels of the soluble form of ICAM-1 (sICAM-1) released by placental cells were unde tectable when assessed by a specific ELISA. Finally, we investigated t he effect of pro-inflammatory cytokines on placental ICAM-1 expression . Treatment of cultured trophoblasts for 24 h with interleukin-1 beta (1 ng/ml or tumor necrosis factor alpha (1 ng/ml) increased surface ex pression of ICAM-1 without inducing sICAM-1 shedding. However, on plac ental cells, the two cytokines exerted stimulatory effects lower than those detected on endometrial cells used as positive control. These ob servations document that the ICAM-1 gene is expressed in both cytotrop hoblasts and syncytiotrophoblasts, suggesting that the molecule may be of value for some immune-mediated processes. On the other hand, the l ow sensitivity of trophoblasts to cytokine-mediated induction of ICAM- 1 expression might represent a functional mechanism contributing to ma ternal tolerance for fetal graft.