Expression of adhesion molecules in human endometrial vasculature throughout the menstrual cycle.

ABSTRACT

In the present study, we examined the pattern of expression of human leukocyte antigen (HLA)-DR as well as several adhesion molecules implicated in leukocyte trafficking, including ICAM-1, E-selectin, and VCAM-1 in human endometrium. All of the vessels in endometrium exhibited HLA-DR and ICAM-1 throughout the menstrual cycle. In the proliferative phase, endothelial cells in the functionalis were weak to nonreactive for VCAM-1 and were E-selectin negative (E-selectin-). Endothelial cells of the vessels in the basalis and within myometrium were VCAM positive (VCAM-1+)/E-selectin-. In sharp contrast, in the secretory phase, endothelial cells in the basalis were VCAM-1+/E-selectin+. Surprisingly, endometrial glands, primarily those in the basalis, expressed E-selectin and VCAM-1 during the entire menstrual cycle. Stromal cells were ICAM-1+ and were focally HLA-DR+ around HLA-DR+ lymphoid cells during the entire menstrual cycle and were E-selectin-/VCAM-1- during the proliferative phase. Immunoreactivity for VCAM-1 and E-selectin, however, appeared in the stromal cells in the upper functionalis in the secretory phase. Immunoreactivity for VCAM-1 was the distinguishing feature that separated the lymphoid cells in the aggregates from other nonaggregated lymphoid cells. Recruitment of leukocytes to tissues is in part due to cytokine-regulated expression of specific molecules on endothelial cells. Therefore, we tested the effects of cytokines on the expression of these molecules in endothelial cells derived from microvasculature. ICAM-1 and VCAM-1 were inducible in a dose-dependent fashion in the endothelial cells by interleukin-1 alpha (IL-1 alpha), interferon-gamma (IFN gamma), and tumor necrosis factor-alpha (TNF alpha). Expression of HLA-DR in endothelial cells was inducible by IL-1 alpha and IFN gamma and not by TNF alpha. Expression of E-selectin on endothelial cells was induced only by IL-1 alpha, not by IFN gamma or TNF alpha. Cytokine treatment of endothelial cells significantly enhanced the binding of leukocytes to endothelial cells. The data show a heterogeneity in the vasculature of endometrium with respect to the expression of various adhesion molecules. This heterogeneity is potentially related to the type or amount of cytokine with which endothelial cells are activated. In addition, unique cell- and site-specific expression of adhesion molecules in human endometrium throughout the menstrual cycle may account for the distinct distribution pattern of leukocytes in this tissue.