EXPRESSION OF ADHESION MOLECULES IN HUMAN ENDOMETRIAL VASCULATURE THROUGHOUT THE MENSTRUAL-CYCLE

In the present study, we examined the pattern of expression of human l eukocyte antigen (HLA)-DR as well as several adhesion molecules implic ated in leukocyte trafficking, including ICAM-1, E-selectin, and VCAM- 1 in human endometrium. Ah of the vessels in endometrium exhibited HLA -DR and ICAM-1 throughout the menstrual cycle. In the proliferative ph ase, endothelial cells in the functionalis were weak to nonreactive fo r VCAM-1 and were E-selectin negative (E-selectin(-)). Endothelial cel ls of the Vessels in the basalis and within myometrium were VCAM posit ive (VCAM-1(+))/E-selectin(-). In sharp contrast, in the secretory pha se, endothelial cells in the basalis were VCAM-1(+)/E-selectin(+). Sur prisingly, endometrial glands, primarily those in the basalis, express ed E-selectin and VCAM-1 during the entire menstrual cycle. Stromal ce lls were ICAM-1(+) and were focally HLA-DR(+) around HLA-DR(+) lymphoi d 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 functio nalis in the secretory phase. Immunoreactivity for VCAM-1 was the dist inguishing 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 m olecules on endothelial cells. Therefore, we tested the effects of cyt okines on the expression of these molecules in endothelial cells deriv ed from microvasculature. ICAM-1 and VCAM-1 were inducible in a dose-d ependent 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-sele ctin on endothelial cells was induced only by IL-1 alpha, not by IFN g amma or TNF alpha. Cytokine treatment of endothelial cells significant ly enhanced the binding of leukocytes to endothelial cells. The data s how a heterogeneity in the vasculature of endometrium with respect to the expression of various adhesion molecules. This heterogeneity is po tentially related to the type or amount of cytokine with which endothe lial cells are activated. In addition, unique cell- and site-specific expression of adhesion molecules in human endometrium throughout the m enstrual cycle may account for the distinct distribution pattern of le ukocytes in this tissue.