title: 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.
abstract: 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.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: M C
authors.initials: MC
authors.lastname: Cid
authors.forename: H K
authors.initials: HK
authors.lastname: Kleinman
authors.forename: D S
authors.initials: DS
authors.lastname: Grant
authors.forename: H W
authors.initials: HW
authors.lastname: Schnaper
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
authors.forename: G S
authors.initials: GS
authors.lastname: Hoffman
mesh_terms: D000273:Adipose Tissue; D001011:Aorta; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol