Smoke and C5a induce airway epithelial intercellular adhesion molecule-1 and cell adhesion

Anthony A. Floreani, Todd A. Wyatt, Julie Stoner, Sam D. Sanderson, Ethan G. Thompson, Diane Allen-Gipson, Art J. Heires

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


The human bronchial epithelial cell is one of the first cell types to be exposed to the irritants and toxins present in inhaled cigarette smoke. The ability of the bronchial epithelium to modulate inflammatory and immune events in response to cigarette smoke is important in the pathogenesis of smoke-induced airway injury. We have shown that cigarette smoke extract and the complement anaphylatoxin C5a both independently induce increased expression of intercellular adhesion molecule (ICAM)-1 on airway epithelial monolayers compared with unstimulated cells in vitro. This enhanced ICAM-1 expression is associated with a greater capacity of the airway epithelial cells to bind mononuclear cells, a process that appears to require the proinflammatory cytokine tumor necrosis factor-α and protein kinase C intracellular signaling. Exposure of epithelial monolayers to the combination of cigarette smoke followed by C5a results in an additive response for ICAM-1 expression and mononuclear cell adhesion compared with smoke or C5a challenge alone. Inhibiting C5a receptor expression can attenuate these responses. These findings suggest that smoke exposure in some way enhances the functional responsiveness of the C5a receptor expressed on these airway epithelial cells for subsequent C5a-mediated increases in ICAM-1 expression and mononuclear cell adhesion. Our results may help explain the initiation and propagation of inflammatory events in vivo induced by chronic airway exposure to cigarette smoke.

Original languageEnglish (US)
Pages (from-to)472-482
Number of pages11
JournalAmerican journal of respiratory cell and molecular biology
Issue number4
StatePublished - Oct 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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