Advanced glycation end products (AGEs) activate mast cells

摘要: BACKGROUND AND PURPOSE Advanced glycation endproducts (AGEs) represent one of the many types chemical modifications that occur with age in long-lived proteins. AGEs also accumulate pathologies such as diabetes, cardiovascular diseases, neurodegeneration and cancer. Mast cells are major effectors acute inflammatory responses contribute to progression chronic diseases. Here we investigated interactions between mast cells. EXPERIMENTAL APPROACHES Histamine secretion from AGEs-stimulated was measured. Involvement a receptor for AGEs, RAGE, assessed by PCR, immunostaining use inhibitors RAGE. Production reactive oxygen species (ROS) cytokines measured. KEY RESULTS dose-dependently induced cell exocytosis maximal effects being obtained within 20 s. RAGE mRNA detected intact were immunostained specific anti-RAGE monoclonal antibody. AGEs-induced inhibited an antibody low molecular weight heparin, known antagonist. expression levels unaltered after 3 h treatment AGEs. AGE-RAGE signalling involves Pertussis toxin-sensitive Gi-proteins intracellular Ca2+ increases pretreatment toxin, caffeine, 2-APB BAPTA-AM AGE-induced exocytosis. rapidly stimulated ROS production. After 6 h pattern cytokine compared controls. CONCLUSIONS IMPLICATIONS activated may vicious cycle involving generation ROS, increased formation activation low-grade inflammation typical