Expression of functional VCAM-1 by cultured nasal polyp-derived microvascular endothelium

Am J Pathol. 1997 Jun;150(6):2113-23.

Abstract

Induction of endothelial vascular cell adhesion molecule-1 (VCAM-1) by interleukin (IL)-4 is believed to exert a major impact on the extravasation of leukocyte subsets in allergic disease. This notion has recently been challenged because cultured microvascular endothelial cells (ECs) derived from various organs are unable to express VCAM-1 after exposure to IL-4. In this study, we have established a method for isolation and culture of nasal polyp-derived microvascular ECs and report their cytokine-regulated VCAM-1 expression. With a combination of cell enzyme-linked immunosorbent assay, flow cytometry, and reverse transcription polymerase chain reaction, such expression was shown to be induced in a dose- and time-dependent manner not only by IL-1 beta and tumor necrosis factor-alpha but also by IL-4 and IL-13. Therefore, the response of nasal microvascular ECs did not harmonize with that of counterparts from several other tissues. IL-4 or IL-13 combined with submaximal concentrations of IL-1 beta or tumor necrosis factor-alpha increased VCAM-1 expression in a synergistic manner. VCAM-1 was functional as shown by antibody-mediated inhibition of leukocyte adhesion. Taken together, our results supported the notion that selective VCAM-1 induction by IL-4 and IL-13 plays an important role for the preferential recruitment of eosinophils and T lymphocytes seen in human airways affected by allergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Burkitt Lymphoma / metabolism
  • Cadherins / metabolism
  • Cell Adhesion / drug effects
  • Cell Culture Techniques / methods
  • Cells, Cultured
  • Cyclic AMP / pharmacology
  • Cytokines / pharmacology*
  • Endothelial Growth Factors / pharmacology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Immunohistochemistry
  • Interleukins / pharmacology
  • Lymphokines / pharmacology
  • Microcirculation / metabolism*
  • Nasal Polyps / blood supply
  • Nasal Polyps / metabolism*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Time Factors
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / metabolism*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • von Willebrand Factor / metabolism

Substances

  • Antigens, CD
  • Cadherins
  • Cytokines
  • Endothelial Growth Factors
  • Interleukins
  • Lymphokines
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • cadherin 5
  • von Willebrand Factor
  • Cyclic AMP