Vortex-mediated mechanical stress induces integrin-dependent cell adhesion mediated by inositol 1,4,5-trisphosphate-sensitive Ca2+ release in THP-1 cells

Noboru Ashida, Hajime Takechi, Toru Kita, Hidenori Arai

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20 Citations (Scopus)


In the downstream regions of stenotic vessels, cells are subjected to a vortex motion under low shear forces, and atherosclerotic plaques tend to be localized. It has been reported that such a change of shear force on endothelial cells has an atherogenic effect by inducing the expression of adhesion molecules. However, the effect of vortex-induced mechanical stress on leukocytes has not been investigated. In this study, to elucidate whether vortex flow can affect the cell adhesive property, we have examined the effect of vortex-mediated mechanical stress on integrin activation in THP-1 cells, a monocytic cell line, and its signaling mechanisms. When cells are subjected to vortex flow at 400-2,000 rpm, integrin-dependent cell adhesion to vascular cell adhesion molecule-1 or fibronectin increased in a speed- and time-dependent manner. Next, to examine the role of Ca2+ in this integrin activation, various pharmacological inhibitors involved in Ca2+ signaling were tested to inhibit the cell adhesion. Pretreatment of cells with BAPTA-AM, thapsigargin +NiCl2, or U-73122 (a phospholipase C inhibitor) inhibited cell adhesion induced by vortex-mediated mechanical stress. We also found that W7 (a calmodulin inhibitor) blocked the cell adhesion. However, pretreatment of cells with GdCl3, NiCl2, or ryanodine did not affect the cell adhesion. These data indicate that vortex-mediated mechanical stress induces integrin activation through calmodulin and inositol 1,4,5-trisphosphate-mediated Ca2+ releases from intracellular Ca2+ stores in THP-1 cells.

Original languageEnglish
Pages (from-to)9327-9331
Number of pages5
JournalJournal of Biological Chemistry
Issue number11
Publication statusPublished - 14-03-2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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