Miserocchi G, Sancini G, Mantegazza F, Chiappino Gerolamo
Department of Experimental Medicine, University of Milano-Bicocca, Via Cadore 48, 20052, Monza, Italy.
Environ Health. 2008 Jan 24;7:4. doi: 10.1186/1476-069X-7-4.
We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption) and hydraulic (interstitial pressure is subatmospheric) pressure gradient. Fibers can be dragged from the lung interstitium by pulmonary lymph flow (primary translocation) wherefrom they can reach the blood stream and subsequently distribute to the whole body (secondary translocation). Primary translocation across the visceral pleura and towards pulmonary capillaries may also occur if the asbestos-induced lung inflammation increases pulmonary interstitial pressure so as to reverse the trans-mesothelial and trans-endothelial pressure gradients. Secondary translocation to the pleural space may occur via the physiological route of pleural fluid formation across the parietal pleura; fibers accumulation in parietal pleura stomata (black spots) reflects the role of parietal lymphatics in draining pleural fluid. Asbestos fibers are found in all organs of subjects either occupationally exposed or not exposed to asbestos. Fibers concentration correlates with specific conditions of interstitial fluid dynamics, in line with the notion that in all organs microvascular filtration occurs from capillaries to the extravascular spaces. Concentration is high in the kidney (reflecting high perfusion pressure and flow) and in the liver (reflecting high microvascular permeability) while it is relatively low in the brain (due to low permeability of blood-brain barrier). Ultrafine fibers (length < 5 mum, diameter < 0.25 mum) can travel larger distances due to low steric hindrance (in mesothelioma about 90% of fibers are ultrafine). Fibers translocation is a slow process developing over decades of life: it is aided by high biopersistence, by inflammation-induced increase in permeability, by low steric hindrance and by fibers motion pattern at low Reynolds numbers; it is hindered by fibrosis that increases interstitial flow resistances.
我们基于肺和胸膜-肺间质液动力学来讨论吸入石棉纤维的转运。由于渗透（主动吸收钠离子）和液压（间质压力低于大气压）压力梯度的共同作用，纤维可以通过细胞旁途径顺着大量水流穿过肺泡屏障并到达肺间质。纤维可被肺淋巴流从肺间质中带走（初次转运），由此它们可进入血流并随后分布至全身（二次转运）。如果石棉诱导的肺部炎症增加了肺间质压力，从而逆转跨间皮和跨内皮的压力梯度，那么也可能发生纤维穿过脏层胸膜并向肺毛细血管的初次转运。纤维通过穿过壁层胸膜形成胸膜液的生理途径可发生向胸膜腔的二次转运；纤维在壁层胸膜气孔（黑点）中的积聚反映了壁层淋巴管在引流胸膜液中的作用。在职业性接触或未接触石棉的受试者的所有器官中都能发现石棉纤维。纤维浓度与间质液动力学的特定条件相关，这与在所有器官中都存在从毛细血管到血管外间隙的微血管滤过这一观点一致。在肾脏（反映高灌注压力和血流量）和肝脏（反映高微血管通透性）中浓度较高，而在大脑中相对较低（由于血脑屏障的低通透性）。超细纤维（长度<5微米，直径<0.25微米）由于空间位阻小（在间皮瘤中约90%的纤维是超细的），可以移动更远的距离。纤维转运是一个在数十年生命过程中缓慢发展的过程：它受到高生物持久性、炎症诱导的通透性增加、低空间位阻以及低雷诺数下的纤维运动模式的促进；它受到增加间质流动阻力的纤维化的阻碍。
