Effects of distension on airway inflammation and venular P-selectin expression

Aigul Moldobaeva, John Jenkins, Elizabeth M. Wagner

Research output: Contribution to journalArticle

Abstract

We previously have shown in mice and rats, enhanced leukocyte recruitment to airway postcapillary venules after excessive distention imposed by the application of positive end-expiratory pressure. Because P-selectin was shown to be essential for this outcome, we sought to establish an in vitro endothelial cell model and determine the mechanisms whereby mechanical distension alters adhesion molecule expression. P-selectin surface expression on mouse jugular vein endothelial cells exposed to cyclic stretch (5 or 20% elongation for 5 min; Flexercell) were compared with static cells. The larger, pathophysiological regimen of cyclic stretch showed a 54% increase in P-selectin expression after stretch compared with static cells. This response was attenuated but confirmed in tracheal venular endothelium (29% increase). We questioned whether these changes were dependent on increases in intracellular Ca2+ through voltage-gated Ca2+ channels. The stretch-induced increase in P-selectin expression was substantially decreased by pretreatment with the T-type Ca2+ channel inhibitor mibefradil (76% inhibition). Furthermore, when the Cav3.1 T-type Ca2+ channel expression was decreased in both endothelial cell subtypes with specific small-interfering RNA, the distension-induced expression of P-selectin decreased to levels less than that observed in static cells. We conclude that P-selectin expression on systemic venular endothelial cells contributes to a proinflammatory phenotype after mechanical stretch and can be selectively modulated by voltage-gated calcium channel inhibition.

Original languageEnglish (US)
Pages (from-to)L941-L948
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume295
Issue number5
DOIs
StatePublished - Nov 2008

Keywords

  • Positive end-expiratory pressure
  • Tracheal venular endothelial cells
  • Vein endothelial cells

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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