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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/L941    most recent 90447.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moldobaeva, A. Articles by Wagner, E. Search for Related Content PubMed PubMed Citation Articles by Moldobaeva, A. Articles by Wagner, E.

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

Department of Medicine, Johns Hopkins University, Baltimore, Maryland

Submitted 18 August 2008 ; accepted in final form 17 September 2008

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 Ca_v3.1 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.

positive end-expiratory pressure; vein endothelial cells; tracheal venular endothelial cells