Alveolar clearance and retention of inhaled insoluble particles in rats simulated by a model inferring macrophage particle load distributions

作者: Werner Stöber , Paul E Morrow , Wolfgang Koch , Gerd Morawietz

DOI: 10.1016/0021-8502(94)90060-4

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摘要: Abstract This paper presents the description of a revised, physiology-oriented compartmental kinetics (“POCK”) model alveolar clearance and retention biologically insoluble, respirable particles. By postulating deposit-activated maximum macrophage recruitment rate leading to quasi-steady state population on epithelial surface, uses theoretical derivation an exposure-dependent distribution particles in determine total load mobile immobilized macrophages. For this, assumes invariant volume capacity macrophages for particle uptake material-dependent critical that causes loss their inherent mobility. Prior gradual onset mobility decrease, there is range low burdens without impairment. Using independently determined physiological data classical coefficients, as well lifetime turnover by phagocytosis, seems be applicable experimental results obtained rats. A constant set parameters minimum three material-dependent, physiologically meaningful variables were sufficient simulate lung burden available lymph node 15 different subchronic or chronic exposures Fischer 344 rats diesel soot, carbon black xerographic toner. deposition rates, predicts establishment states pool. The final would increase with increasing and, particularly under overload conditions, i.e. at high number grow significantly. According model, does not cause excessive growth pool, but leads tremendous particulate interstitial space. macrophage-mediated clearance. Except partial removal nodes, will persist even when are discontinued recovers full Subchronic exposure studies seem bear this out, due lack most subcompartments corresponding predictions cannot validated present time.

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