Bhalla D K, Lavan S M, Crocker T T
Department of Community and Environmental Medicine, University of California, Irvine 92717.
Exp Lung Res. 1988;14(4):501-25. doi: 10.3109/01902148809087824.
Ozone (O3) exposure of rats increases airway epithelial permeability. We hypothesized that this increased permeability may be mediated by the epithelial cell cytoskeleton. To test this hypothesis, we studied the effect of cytoskeletal disruption on the transmucosal transport of tracers from airway lumen to blood and compared the results with the effects of O3 exposure. No increase in transport occurred following disruption of microtubules by vinblastine, but disruption of microfilaments with cytochalasin D resulted in increased transport of radiolabeled tracers [99mTc- and 111In-labeled diethylenetriamine-pentacetate (DTPA) and 125I-labeled bovine serum albumin (BSA)]. In control rats, both horseradish peroxidase (HRP) and BSA, localized by cytochemistry and autoradiography, respectively, were detected on the epithelial cell surfaces and in endocytic vesicles. In rats treated with cytochalasin D or exposed to O3, the tracer molecules also penetrated the intercellular spaces, though the apical tight junctions remained devoid of the tracers. Increased numbers of endocytic vesicles containing HRP and aggregation of 125I-labeled BSA autoradiographic grains in the subepithelial region were also seen after either treatment. We conclude that destabilization of cytoskeletal elements following O3 exposure is a possible mechanism of increased transmucosal transport, which may be a combined effect of accelerated transport through both endocytic and paracellular pathways.
大鼠暴露于臭氧（O₃）会增加气道上皮通透性。我们推测这种通透性增加可能由上皮细胞细胞骨架介导。为验证这一假说，我们研究了细胞骨架破坏对示踪剂从气道腔向血液跨黏膜转运的影响，并将结果与臭氧暴露的影响进行比较。长春碱破坏微管后转运未增加，但细胞松弛素D破坏微丝导致放射性标记示踪剂[⁹⁹ᵐTc和¹¹¹In标记的二乙烯三胺五乙酸（DTPA）以及¹²⁵I标记的牛血清白蛋白（BSA）]的转运增加。在对照大鼠中，分别通过细胞化学和放射自显影定位的辣根过氧化物酶（HRP）和BSA在上皮细胞表面和内吞小泡中均有检测到。在用细胞松弛素D处理或暴露于臭氧的大鼠中，示踪剂分子也穿透了细胞间隙，尽管顶端紧密连接仍无示踪剂。两种处理后还可见到含有HRP的内吞小泡数量增加以及¹²⁵I标记的BSA放射自显影颗粒在基底上皮区域聚集。我们得出结论，臭氧暴露后细胞骨架成分的不稳定是跨黏膜转运增加的一种可能机制，这可能是通过内吞和细胞旁途径加速转运的综合作用。
