Universidad Austral de Chile, Valdivia, Chile.
Res Vet Sci. 2012 Feb;92(1):103-10. doi: 10.1016/j.rvsc.2010.10.005. Epub 2010 Nov 10.
This study describes the effect of 2-aminoethoxydiphenyl borate (2-APB), a putative store-operated calcium (Ca(2+)) entry (SOCE) inhibitor, on reactive oxygen species (ROS) production, matrix metalloproteinase 9 (MMP-9) release, CD11b and l-selectin (CD62L) expression, size changes and apoptosis in bovine neutrophils stimulated with platelet-activating factor (PAF). It was observed that doses ⩾1μM 2-APB significantly reduced ROS production, whereas 50 and 100μM 2-APB reduced MMP-9 release induced by PAF. Moreover, concentrations ⩾10μM 2-APB reduced CD11b expression and increased l-selectin shedding. PAF induced size changes in neutrophils, and this effect was inhibited by 2-APB. From this work it is possible to conclude that 2-APB at concentrations that inhibit SOCE responses was able to inhibit ROS and MMP-9 release and CD11b expression, and increase l-selectin shedding, suggesting that the Ca(2+) channel involved in SOCE is a potential target for the development of new anti-inflammatory drugs in cattle.
本研究描述了 2-氨基乙氧基二苯硼酸盐(2-APB)对活性氧物种(ROS)产生、基质金属蛋白酶 9(MMP-9)释放、CD11b 和 l-选择素(CD62L)表达、牛嗜中性粒细胞大小变化和凋亡的影响,这些细胞被血小板激活因子(PAF)刺激。结果表明,剂量≥1μM 的 2-APB 可显著减少 ROS 的产生,而 50 和 100μM 的 2-APB 可减少 PAF 诱导的 MMP-9 释放。此外,浓度≥10μM 的 2-APB 可降低 CD11b 的表达并增加 l-选择素脱落。PAF 诱导嗜中性粒细胞大小变化,2-APB 可抑制这种作用。从这项工作中可以得出结论,抑制 SOCE 反应的 2-APB 浓度能够抑制 ROS 和 MMP-9 的释放以及 CD11b 的表达,并增加 l-选择素脱落,表明参与 SOCE 的 Ca(2+)通道可能是牛开发新型抗炎药物的潜在靶点。