Expression and regulation of intercellular adhesion molecule-1 on airway parasympathetic nerves

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: Eosinophils cluster along airway nerves in patients with asthma and release eosinophil major basic protein, an antagonist of inhibitory M2 muscarinic receptors on nerves. Blocking M2 function increases bronchoconstriction, leading to airway hyperreactivity. Intercellular adhesion molecule-1 (ICAM-1) mediates eosinophil adhesion to nerves. Objective: We investigated mechanisms of ICAM-1 expression by parasympathetic nerves. Methods: ICAM-1 expression was examined by immunocytochemistry of lung sections from ovalbumin-sensitized and challenged guinea pigs. ICAM-1 was measured in parasympathetic nerves isolated from subjects and guinea pigs and in human neuroblastoma cells by real-time RT-PCR, immunocytochemistry, and Western blot. Results: ICAM-1 was not detected in control airway parasympatheric nerves in vivo or in cultured cells. ICAM-1 was expressed throughout antigen-challenged guinea pig lung tissue and was selectively decreased by dexamethasone only in nerves. ICAM-1 was induced in human and guinea pig parasympathetic nerves by TNF-α and IFN-γ and was inhibited by dexamethasone and by an inhibitor of nuclear factor-κB (NF-κB). In neuroblastoma cell lines TNF-α and IFN-γ-induced ICAM-1 was blocked by an inhibitor of NF-κB but not by inhibitors of mitogen-activated protein kinases. Dexamethasone did not inhibit ICAM-1 expression in neuroblastoma cells. Conclusions: ICAM-1 induced in nerves by antigen challenge and proinflammatory cytokines is sensitive to dexamethasone. ICAM-1 expression is also sensitive to inhibitors of NF-κB. Neuroblastoma cells mimic many, but not all, characteristics of ICAM-1 expression in parasympathetic nerves. Clinical implications: Dexamethasone and NF-κB inhibitors could prevent eosinophils from adhering to nerves by blocking ICAM-1 expression on parasympathetic nerves, thus protecting inhibitory M2 muscarinic receptors and making this pathway a potential target for asthma treatment.

Original languageEnglish (US)
Pages (from-to)1415-1422
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume119
Issue number6
DOIs
StatePublished - Jun 1 2007

Keywords

  • Intercellular adhesion molecule 1
  • TNF-α
  • asthma
  • dexamethasone
  • guinea pig
  • human
  • nuclear factor κB
  • parasympathetic nerve

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Expression and regulation of intercellular adhesion molecule-1 on airway parasympathetic nerves'. Together they form a unique fingerprint.

  • Cite this