Expression of adhesion molecules in human endometrial vasculature throughout the menstrual cycle
S Tabibzadeh, QF Kong and A Babaknia
Department of Pathology, University of South Florida Health Sciences Center, Tampa 33612.
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.
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