Acidosis in local environment plays a critical role in cell injury. One key mediator of acidosis-induced cell injury is the acid-sensing ion channels (ASICs), particularly ASIC1a. Herein, we investigated the role of ASIC1a in acid-induced vascular endothelial cell injury of Henoch-Schönlein purpura (HSP) children. Acid-induced ASIC1a, Calpain and Calcineurin expression in vascular endothelial cells pretreated with IgA1 isolated from HSP were detected by real time quantitative polymerase chain reaction and western blot methods, respectively. Cell cytotoxicity was measured by interleukin-8 and nitric oxide production with ELISA. The results showed acid-induced ASIC1a, Calpain and Calcineurin expression in cells increased, especially at PH6.5. The cytotoxicity of vascular endothelial cells was increased by extracellular acidosis. Moreover non-specific or specific blockers of ASIC1a, Amiloride and PcTX-1 could remarkably decrease these parameters. These findings show that increased [Ca 2+ ]i, mediated via ASIC1a, might contribute to acid-induced vascular endothelial cell injury of HSP.

BackgroundHenoch-Schönlein Purpura (HSP) is a common small vessel vasculitis in children which is characterized by non-thrombocytopenic purpura, arthritis, bowel angina and glomerulonephritis [1]. It is generally accepted that immunoglobulin A (IgA), especially IgA1 and complement C3 deposited in the walls of arterioles, capillaries, and venules, immune inflammatory reaction are involved in the vascular endothelial cell injury of HSP patients [1-3]. In the majority of cases, HSP is a self-limiting disease and treatment is supportive. However, HSP has a high rate of recurrence, and some patients can progress to HSP nephritis (HSPN), which can result in renal failure [4]. Up to now, there is no effective therapy to impede these events to occur. So it is extremely urgent to further research on the pathophysiology of HSP.Acid-sensing ion channels (ASICs) are cationic channels which belong to the degenerin/ epithelial Na + channel (DEG/ENaC)