Development of a multicompartmental model of the kinetics of quartz dust in the pulmonary region of the lung during chronic inhalation exposure of rats.

Abstract

A multicompartmental model for the kinetics of dust retention in the pulmonary region of the lung and in the tracheobronchial lymph nodes has been developed. The model reflects the following ideas concerning the basic features ofthis process: (1) penetration into the pulmonary interstitium and translocation to the lymph nodes are possible for nonphagocytised particles only; (2) these processes depend on the degree of damage to macrophages by dust and on the extent of compensatory enhancement in the recruitment of neutrophils taking part in the clearance of the pulmonary region free surface; (3) a certain proportion of initially penetrating particles is continuously returned to this surface together with recruited pulmonary macrophages. The model ensures a satisfactory approximation to experimental data on the retention ofquartz in the lung and lymph nodes during long term inhalation exposure, and simulation of the kinetic effects associated with both the damage to and the protection of the macrophagal clearance mechanism.Various mathematical models for the kinetics of deposition and retention of dust in the lung are usually proposed as a basis for predicting "the accumulation of lung burden during prolonged chronic exposure relevant to the exposure of workers to mineral dusts in a wide range of industries"' and, thus, as an instrument for "exposure assessment for occupational epidemiology".23Another Modelling the kinetics of the deposition and retention of particles in the "deep lung" (meaning the region that was called "pulmonary" by the ICRP Task Group on Lung Dynamics4 and many other authors) Vincent et al considered two mutually independent compartments of "medium" and "slow" clearance; the third compartment (of "fast" clearance) corresponded to the tracheobronchial region. The model, however, does not account for the physiological mechanisms that determine the differences in the rate of clearance of the compartments, and its structure is not claimed to describe actual relations between them.Most investigators (for example5) identify the rapidly removed part of dust deposited in the pulmonary region as that which is removed directly from the free surface ofthe acinus towards the mucociliary escalator, and the slowly removed part as that which has already penetrated into the "fixed tissues" (into the lung interstitium). Thus in both the route of deposition and the route of elimination, real compartments of dust in the "deep lung" are connected in series rather than in parallel as in the model.'One ofthe variants ofthis model assumes a sudden and complete failure of the medium clearance compartment and, therefore, transfer of all material into the slow clearance compartment. In another variant of the same model, both compartments have parallel exits not only to the mucociliary escalator but also to some intralung kinetic trap that has no exit at all. Like the basic model,' both of these variants ensure a

Some Peculiarities of Pulmonary Clearance Mechanisms in Rats after Intratracheal Instillation of Magnetite (Fe3O4) Suspensions with Different Particle Sizes in the Nanometer and Micrometer Ranges: Are We Defenseless against Nanoparticles?

“…Cell dimensions varied from 7.5 to 35 µm. It is possible to see that the number of micropits on the surfaces of cells that were in contact in vivo with magnetite particles is much greater than in the control group and that Note: The original model that had no upward arrows signifying hypothetical dissolution/resorption pathways of pulmonary clearance was developed, identified, and successfully tested on different experimental data by Katsnelson et al [36][37][38] for a mathematical description of processes controlling translocation, elimination, and retention of virtually insoluble dust particles. Here: µu is a function of particle deposition in the pulmonary region, and k ji is a transfer rate constant, that is, the probability of particle translocation from compartment X i into compartment X j .…”

“…A mathematical multicompartmental model of pulmonary region clearance which describes just this compensatory mechanism simulates very well the retention of dusts of varying degree of cytotoxicity (quartzite rock, titanium dioxide, and standard quartz [DQ12]) in the lungs in long-term inhalation and a decrease in this retention under the effect of such potent protectors of the macrophage against the cytotoxicity of particles as glutamate. [36][37][38] We added arrows to the diagram representing the structure of this model (Figure 11), showing the clearance of the pulmonary region from particles as a result of their dissolution, which can presumably take place in any of the compartments.…”

Prediction of the comparative intensity of pneumoconiotic changes caused by chronic inhalation exposure to dusts of different cytotoxicity by means of a mathematical model.

“…Therefore we use the model that was proposed previously for describing just kinetic processes directly or indirectly associated with the phagocytosis of particles and the resulting breakdown of lung macrophages. 5 This model makes it possible to explicitly simulate differences due to unequal cytotoxicity of the dusts under comparison. It is also possible to check whether such simulation would be sufficient for predicting the accumulation of these dusts in the lung parenchyma and in tracheobronchial lymph nodes during chronic inhalation and after a long period of recovery after exposure.…”

Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview)

“…It is well-known that important qualitative and quantitative patterns of the response of the pulmonary free cell population (in particular, its dependence on the cytotoxicity of deposited particles) observed in inhalation exposures to dust particles are principally the same in the case of their IT administration. 77 At the same time, IT model provided cellular material for studying the phagocytizing activity of pulmonary macrophages and polymorphonuclear leukocytes, as well as intracellular localization of NPs engulfed by them and ultrastructural damage caused to the cell by those NPs. The results thus obtained are comparable to the data obtained by other researchers in experiments on cell cultures but give a valuable addition to the latter because in vivo interaction between cells and particles occurs in a microenvironment which is not reproducible by artificial cell culture media.…”