Th1-and Th2-type lymphokine-assisted induction and release of chemokine receptors from primary human trophoblast cells

Chemokine receptors (CCRs) have been demonstrated to facilitate the entry of HIV in different cell types of infected individuals, including CD4(+) T cells and dendritic cells. The natural or inducible expression of CCRs on trophoblast cells could provide a valid mechanism for the ill utero transmission of HIV from mother to fetus. Because of the rapid turnover of these receptors, ive attempted to define the natural and inducible expression of surface CCR3 and CXCR4 on primary human trophoblasts during short periods of cell culture. In the absence of any external stimulus the expression of CCR3 and CXCR4 varied from 1% to 24%. Kinetic experiments show that the levels of both CCR3 and CXCR4 reach a peak of expression after 6 h of culture, whereas by 24 h they have almost disappeared. In the presence of IFN-gamma, CCR3 is showing an increasing pattern of expression after 4 h of incubation, reaching highest levels after 24 h of culture, whereas CXCR4 is kept at lower levels as compared with nontreated cells. Furthermore, in the presence of IL-4, CCR3 expression declines from 2 to 8 h of culture to increase again at 24 h, where 50% of the cell population is expressing the receptors, Under the IL-4 stimulus, CXCR4 shows a peak of expression at 8 h of culture. An interesting feature of this study is that we were able to detect soluble CCR activity in the culture supernatants of trophoblast cells, which followed an inverse pattern of this of surface expression. Thus, the inability of many laboratories to detect high levels of CCRs in placentae of HIV infected mothers may be due on these fast turnover of these receptors, which by the assaying time have either been released in the culture medium or been internalized to the cell. Human Immunology 61, 651-657 (2000). (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.