Estradiol enhances leukocyte binding to tumor necrosis factor (TNF)-stimulated endothelial cells via an increase in TNF-induced adhesion molecules E-selectin, intercellular adhesion molecule type 1, and vascular cell adhesion molecule type 1

• Published in: The Journal of clinical investigation Vol. 93; no. 1; pp. 17 - 25
• Main Authors: CID, M. C, KLEINMAN, H. K, GRANT, D. S, SCHNAPER, H. W, FAUCI, A. S, HOFFMAN, G. S
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 1994
• Subjects: Adipose Tissue; Analysis of the immune response. Humoral and cellular immunity; Aorta; Biological and medical sciences; Cell Adhesion - drug effects; Cell Adhesion Molecules - biosynthesis; Cell Adhesion Molecules - physiology; Cells, Cultured; Dose-Response Relationship, Drug; E-Selectin; Endothelium - drug effects; Endothelium - physiology; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Estradiol - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Intercellular Adhesion Molecule-1; Kinetics; Leukocytes - drug effects; Leukocytes - physiology; Lymphokines, interleukins ( function, expression); Monocytes - drug effects; Monocytes - physiology; Neutrophils - drug effects; Neutrophils - physiology; Progesterone - pharmacology; Regulatory factors and their cellular receptors; Testosterone - pharmacology; Tumor Necrosis Factor-alpha - pharmacology; Umbilical Veins; Vascular Cell Adhesion Molecule-1; Immunopathology; Endothelial cell; Leukocyte; Pathogenesis; Estrogen; Cytokine; Cell adhesion molecule; Stimulation; Estradiol; Ovarian hormone; Inflammatory disease; Binding protein; Sex steroid hormone
• DOI: 10.1172/jci116941
• ISSN: 0021-9738

Adhesion of leukocytes to endothelial cells is a critical step in the development of acute and chronic inflammatory lesions. We report here that estradiol treatment of cultured human umbilical vein endothelial cells stimulated up to a twofold increase in TNF-induced adhesion of both polymorphonuclear leukocytes and PMA-activated peripheral blood mononuclear cells. This effect was more evident (threefold increase) when endothelial cells were cultured on the basement membrane glycoprotein laminin. Progesterone, but not testosterone, had a similar stimulatory effect. Estradiol also promoted a slight increase in interferon gamma-stimulated endothelial cell adherence for peripheral blood mononuclear cells, but no effect of estradiol was observed when adhesion of leukocytes to endothelial cells was stimulated with IL-1 or IL-4. The estradiol-induced increase in leukocyte binding to human umbilical vein endothelial cells was partially blocked by antibodies to the adhesion molecules E-selectin, intercellular adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule type 1 (VCAM-1). Indirect immunofluorescence techniques showed that estradiol produces an increase in TNF-induced cell surface expression of these molecules. Northern blot analysis demonstrated a transient increase in TNF-induced expression of mRNA for E-selectin, ICAM-1, and VCAM-1 in endothelial cells treated with estradiol. Our data demonstrate that estradiol has important regulatory functions in promoting leukocyte-endothelial cell interactions that might contribute to the observed predominance in females of some autoimmune inflammatory diseases.