Improvements in endotoxemic syndromes using a disintegrin, rhodostomin, through integrin αvβ3-dependent pathway

摘要: Summary. Background and objectives: Septic shock is a major cause of morbidity mortality in intensive care units, but there still no effective therapy for the patients. We evaluated effects rhodostomin (Rn), an Arg-Gly-Asp-containing snake venom disintegrin, on lipopolysaccharide (LPS)-activated phagocytes vitro LPS-induced endotoxemia vivo. Methods results: Rn inhibited adhesion, migration, cytokine production mitogen-activated protein kinase (MAPK) activation macrophage induced by LPS. Flow cytometric analysis revealed that Rn specifically blocked anti-αv mAb binding to RAW264.7. Besides inhibiting MAPK THP-1, bound LPS-activated THP-1 anti-αvβ3 THP-1. Binding assays proved integrin αvβ3 was site phagocytes. reversed enhancement fibronectin vitronectin monocyte adhesion release. Transfection αv siRNA also monocyte, exerted further inhibitory effect. Furthermore, significantly decreased tumor necrosis factor-α (TNF-a), interleukin (IL)-6, -1β -10 attenuated cardiovascular dysfunction, including blood pressure heart pulse, thrombocytopenia endotoxemic mice. protected against tissue inflammation as evidenced histological examination. Conclusions: Rn may interact with monocytes/macrophages leading interfere triggered These results suggest protective function be attributed its anti-inflammation activities