Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells

Toshiaki Sendo, Tomoko Sumimura, Yoshinori Itoh, Takeshi Goromaru, Keisei Aki, Takahisa Yano, Masahiro Oike, Yushi Ito, Shuji Mori, Masahiro Nishibori, Ryozo Oishi

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Abstract

We report here a direct modulation by mast cell tryptase of endothelial barrier function through activation of proteinase-activated receptor-2 (PAR-2). In cultured bovine aortic endothelial cells (BAECs), tryptase, trypsin and PAR-2 activating peptide impaired the barrier function as determined by the permeability of protein-conjugated Evans blue. The tryptase-induced barrier dysfunction was completely blocked by U73122, and partially reversed by xestospongin C, calphostin C or Y27632. The intracellular Ca2+ was elevated by tryptase. It was notable that ioxaglate, a contrast material that degranulates mast cells, markedly increased the permeability when applied to BAECs in combination with mast cells, an action that was blocked by nafamostat, a potent tryptase inhibitor. Immnofluorescence analysis showed that actin stress fibre formation and disruption of VE-cadherin were observed after exposure to tryptase or ioxaglate in combination with mast cells. Therefore, it is suggested that mast cell tryptase impairs endothelial barrier function through activation of endothelial PAR-2 in a manner dependent on the phospholipase C activity.

Original languageEnglish
Pages (from-to)773-781
Number of pages9
JournalCellular Signalling
Volume15
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

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Keywords

  • Actin stress fibre
  • Bovine aortic endothelial cells
  • Mast cell tryptase
  • Nafamostat
  • Proteinase-activated receptor-2
  • VE-cadherin

ASJC Scopus subject areas

  • Cell Biology

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