Lonky S A, Wohl H
J Clin Invest. 1981 Mar;67(3):817-26. doi: 10.1172/JCI110099.
The purpose of this study was to determine if human platelet factor 4 (PF4) stimulates human leukocyte elastase (HLE) against lung elastin. Lung elastin was purified from hamster lungs and tritiated by reduction with NaB3H4. We found that HLE activity against this substrate is increased by concentrations of PF4 as low as 1.6 microgram/ml, and that this stimulation increased linearly with additional PF4. Lungs removed from hamsters and inflated with solutions containing buffer alone, low dose HLE, HLE plus PF4, or PF4 alone were incubated for 2 h at 37 degrees C. Whereas low-dose HLE failed to lower lung elastin when compared to control animals, HLE stimulated by PF4 lowered lung elastin by 20%. PF4 alone had no effect. Furthermore, low-dose HLE failed to alter the mechanical properties of hamster lungs as measured by pressure-volume curves in saline, although there was a significant loss of lung elasticity in the mid- and high-lung volume ranges in lungs treated with HLE and PF4. Morphologic studies revealed that low dose HLE resulted in a minimal emphysemalike lesion whereas HlE plus PF4 caused a significantly more severe lesion. PF4 is capable of stimulating HLE against lung elastin, and this effect may have a role in the pathogenesis of emphysema.
本研究的目的是确定人血小板因子4（PF4）是否刺激人白细胞弹性蛋白酶（HLE）作用于肺弹性蛋白。从仓鼠肺中纯化肺弹性蛋白，并用NaB3H4还原进行氚标记。我们发现，低至1.6微克/毫升的PF4浓度即可增加HLE对该底物的活性，并且这种刺激随着PF4的增加呈线性增加。从仓鼠身上取出的肺，用仅含缓冲液、低剂量HLE、HLE加PF4或仅含PF4的溶液充气后，在37℃孵育2小时。与对照动物相比，低剂量HLE未能降低肺弹性蛋白，但PF4刺激的HLE使肺弹性蛋白降低了20%。单独的PF4没有效果。此外，低剂量HLE未能改变仓鼠肺在盐水中通过压力-容积曲线测量的力学性能，尽管在用HLE和PF4处理的肺中，肺弹性在中高肺容积范围内有显著损失。形态学研究表明，低剂量HLE导致最小程度的类肺气肿病变，而HLE加PF4则导致明显更严重的病变。PF4能够刺激HLE作用于肺弹性蛋白，这种作用可能在肺气肿的发病机制中起作用。
