Immunohistochemical analysis of β1-integrin receptors displayed by murine uterine natural killer cells over the course of successful pregnancy

Abstract

Granulated metrial gland (GMG) cells are a natural killer (NK) cell-like population present in large numbers in the pregnant rodent uterus. By day 8 of gestation GMG cells are large and granulated and localized to the mesometrial side of each implantation site. GMG cells appear to be highly migratory both in vivo and in vitro; however, little is known regarding their functions. Using indirect fluorescence immunohistochemistry, murine uteri and implantation sites were studied on successive days of gestation to characterize the extracellular matrix receptors of the VLA-integrin family displayed by GMG cells. On days 3 and 6 of gestation, double immunostaining using the monoclonal antibody LGL-1 was employed to recognize GMG cells because their morphology early in pregnancy resembles that of other lymphocytes. Between days 8–15 of gestation, GMG cells can be recognized by their unique morphology. The day 3 and day 6 LGL-1 + cells were positive for all antigens examined; that is, β1 plus α1, α3, α4, α5 and α6. From days 8–15 of gestation, GMG cells were β1 +, α4 +, α5 + but α1 −, α3 −, α6 −. Thus, between days 6–8 of gestation, major changes occur in the uterine NK/GMG cell population which include the loss of the surface molecules VLA α1, α3 and α6 or the rapid expansion of NK cells not expressing these proteins. It is postulated that major changes in the functions of uterine NK cells are likely to be associated with these alterations in cell surface phenotype and that functional studies of uterine NK cells should focus upon this relatively early gestational time point.