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

Maria C. Cid, Hynda K. Kleinman, Derrick S. Grant, H. William Schnaper*, Anthony S. Fauci, Gary S. Hoffman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

214 Scopus citations

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 γ-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.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalJournal of Clinical Investigation
Volume93
Issue number1
DOIs
StatePublished - 1994

Keywords

  • cytokines
  • endothelial cell
  • estrogen
  • inflammation
  • vasculitis

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this