Endothelial cell apoptosis is an early event in the development of acute lung injury (ALI). We have previously found that the Src family tyrosine kinase (STK) yes activates caspase-3, while the STK fyn inhibits caspase-3 activation in cultured pulmonary endothelial cells. We hypothesized that deficiency in yes or fyn in mice would have differential effects on lipopolysaccharide (LPS)-induced ALI. Mice were treated with 10 mg/kg LPS i.p. for 24 hours. Histological evidence of lung injury was greater in LPS-treated wild-type mice than in vehicle treated wild-type mice, and the LPS-induced histological evidence of lung injury were attenuated in yes^-/- mice and enhanced in fyn^-/- mice. In wild-type or fyn^-/- mice LPS resulted in greater lung wet-to-dry weight ratios than in controls, while in yes^-/- mice lung wet-to-dry weight was similar between LPS and controls. LPS-exposed fyn^-/- mice had greater respiratory system resistance and lower respiratory system compliance than did LPS-exposed wild-type mice. TUNEL positive cells in the lung following LPS treatment were greater in the fyn^-/- mice and lower in the yes^-/- mice compared to that in the wild-type mice. Following LPS treatment lung protein levels of PECAM-1 were lower in fyn^-/- mice than in controls or yes^-/- mice. LPS treatment increased cleaved caspase-3 protein levels in wild-type mice, while LPS-induced caspase-3 activation was attenuated in yes^-/- mice and enhanced in fyn^-/- mice. These results indicate that LPS-induced ALI is positively mediated via yes related mechanisms and negatively mediated by fyn related mechanisms.

中文翻译：

---

Src家族酪氨酸激酶yes和fyn对脂多糖诱导的小鼠肺损伤的不同影响

内皮细胞凋亡是急性肺损伤（ALI）发展的早期事件。我们之前发现 Src 家族酪氨酸激酶 (STK) yes 激活 caspase-3，而 STK fyn 抑制培养的肺内皮细胞中 caspase-3 的激活。我们假设小鼠中yes 或fyn 的缺乏会对脂多糖（LPS）诱导的ALI 产生不同的影响。用 10 mg/kg LPS ip 处理小鼠 24 小时。在 LPS 处理的野生型小鼠中肺损伤的组织学证据比在载体处理的野生型小鼠中更大，并且 LPS 诱导的肺损伤组织学证据在 yes ^-/-小鼠中减弱并且在 fyn ^-/-小鼠中增强. 野生型或 fyn ^-/-与对照组相比，LPS 导致小鼠肺干湿重比更大，而在是^-/-小鼠中，LPS 和对照组之间的肺湿干重相似。与暴露于 LPS 的野生型小鼠相比，暴露于LPS 的 fyn ^{-/-小鼠具有更大的呼吸系统阻力和更低的呼吸系统顺应性。}与野生型小鼠相比，LPS 处理后肺中的 TUNEL 阳性细胞在 fyn ^-/-小鼠中较多，而在 yes ^{-/-小鼠中较低。}在 LPS 治疗后，fyn ^-/-小鼠的肺蛋白水平 PECAM-1 低于对照组或是^-/-老鼠。LPS 处理增加了野生型小鼠中裂解的 caspase-3 蛋白水平，而 LPS 诱导的 caspase-3 活化在 yes ^-/-小鼠中减弱并且在 fyn ^-/-小鼠中增强。这些结果表明LPS诱导的ALI通过yes相关机制正向介导，并且由fyn相关机制负向介导。