Vortex-mediated Mechanical Stress Induces Integrin-dependent Cell Adhesion Mediated by Inositol 1,4,5-Trisphosphate-sensitive Ca2+ Release in THP-1 Cells

• Published in: The Journal of biological chemistry Vol. 278; no. 11; pp. 9327 - 9331
• Main Authors: Ashida, Noboru, Takechi, Hajime, Kita, Toru, Arai, Hidenori
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 14.03.2003
• Subjects: Calcium - metabolism; Calmodulin - metabolism; Cell Adhesion; Cell Line; Chelating Agents - pharmacology; Dose-Response Relationship, Drug; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Endothelium, Vascular - cytology; Enzyme Inhibitors - pharmacology; Estrenes - pharmacology; Fibronectins - metabolism; Humans; Inositol 1,4,5-Trisphosphate - metabolism; Integrin beta1 - metabolism; Integrins - metabolism; Monocytes - metabolism; Pyrrolidinones - pharmacology; Stress, Mechanical; Sulfonamides - pharmacology; Time Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M212316200

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 Ca 2+ in this integrin activation, various pharmacological inhibitors involved in Ca 2+ signaling were tested to inhibit the cell adhesion. Pretreatment of cells with BAPTA-AM, thapsigargin +NiCl 2 , 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 GdCl 3 , NiCl 2 , 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 Ca 2+ releases from intracellular Ca 2+ stores in THP-1 cells.