[Integrin-ligands binding reaction upregulates the antioxidant activity of rabbit bronchial epithelial cells]

Antioxidant activity of bronchial epithelial cells (BECs) plays an essential role in preventing the airway epithelium integrity from damage in structure and function. Integrin expressed by BECs is the receptor of extracellular matrix such as fibronectin (Fn), and it is involved in modulation of proliferation, differentiation and metabolism of the cells. In order to test the hypothesis that integrin-ligand binding reaction supports the ability of cells to withstand oxidant attack, the present study evaluated the antioxidant activity of primary cultured rabbit BECs treated with fibronectin or its sequence Arg-Gly-Asp (RGD peptide), by determining changes in the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) and in the level of glutathione (GSH). The results are as follows: (1) Fn (10 micrograms/ml) increased significantly the activity unit of GSH-Px (P < 0.05, n = 5), which was inhibited by calmodulin-inhibitor W7 (10(-5) mol/L) (P < 0.05). Both Fn (5-20 micrograms/ml) and RGD (15-60 micrograms/ml) showed a dose-dependent upregulatory effect (respectively r = 0.93 and r = 0.73). (2) Treatment with Fn increased SOD activity (P < 0.01, n = 7), which was abolished by W7 (P < 0.01). (3) Catalase activity was also stimulated by Fn (P < 0.05, n = 6) and reversed by W7 (P < 0.01). (4) A dose-dependent increase of GSH level was observed in both Fn (r = 0.82) and RGD treatment (r = 0.84). The data suggest that the binding of integrin with extracellular matrix can upregulate activity of antioxidant enzymes, and increase the content of GSH and improve the ability of BECs to resist oxidant injury.