Some peculiarities of the pulmonary phagocytotic response: dust retention kinetics and silicosis development during long term exposure of rats to high quartz dust levels.

Abstract

Rats were exposed to quartz dust (about 90 mg/m3) for five hours a day, five times a week either throughout the 48 weeks of the experiment or for a total of 40 weeks plus eight weeks of "rest."Cytological study of bronchoalveolar lavage showed that at a certain level of silicotic changes in the lungs, a pronounced breakdown in pulmonary dust clearance by macrophages could be observed. There was, however, a concomitant compensatory increase in the contribution to pulmonary phagocytosis by the neutrophil leukocytes (NL). As a result, pulmonary dust kinetics could be mathematically described using a constant clearance rate both throughout the 48 weeks of exposure and during the eight weeks after the end of the 40 week exposure. It is shown in a separate experiment that enhanced recruitment of NL into the airways may be due not only to an attractant effect of the products of macrophage breakdown (PMB) themselves but also to the release of an NL attractant factor by viable macrophages activated under influence of the PMB.

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)

“…They are hardly always living with chronic inflammation of the respiratory system. Meantime, it is long ago that we [96][97][98][99][100] found fairly strong reasons for considering the NL recruitment response to be an important mechanism of partial compensation for the damage caused by cytotoxic micrometric particles to AMs, the main effector of the pulmonary clearance. A mathematical multi-compartmental model of pulmonary region clearance which comprised just this compensatory mechanism simulated very well the pulmonary retention of dusts of varying degrees of cytotoxicity (quartzite rock, titanium dioxide, standard quartz DQ12) under long-term inhalation exposure as well as a decrease in this retention under the effect of such potent protectors of the macrophage against particle cytotoxicity as glutamate.…”

“…It was found that this recruitment is controlled by the mass of macrophage breakdown products (MBP) and especially by their lipid fraction. [96][97][98][99][100] Therefore, the more cytotoxic for AMs are particles deposited in the lungs (or the higher the dose of MBPs obtained by aseptic freezingthawing or ultrasonic destruction of non-activated peritoneal macrophages and then instilled intratracheally), the higher is a count ratio of NLs to AMs in the BALF. Therefore this ratio (NL/AM) can be used as an indirect but highly informative comparative in vivo index for the cytotoxic action of any low-soluble particle, and it was demonstrated that ranking of dusts by this index was well correlated with the ranking of their cytotoxicity based on the Trypan blue exclusion test for cell viability in vitro.…”

Trends and Perspectives of the Biological Prophylaxis of Silicosis

“…A special mathematical analysis (55) and a long-term inhalation experiment corroborating its conclusions (25,56) demonstrated that such a dependece really exists. As concerns prophylactic efficiency of the defense with time factor against silicosis, those conclusion are briefly as follows.…”

“…Experimental data that demonstrate that this damage is partly compensated by enhanced contribution of neutrophil leukocytes to phagocytosis of cytotoxic particles and, thus, to their clearance from lungs, have been summarized previously (24). Later it was shown that the role of this compensatory mechanism became still more important under long-term quartz dust inhalation exposure (25). When the development of silicosis in lungs of exposed rats reached a certain level, the macrophage mechanism of phagocytosis became so grossly damaged that the dif-ference between bronchoalveolar lavage (BAL) macrophage counts of exposed and control rats, quite considerable at early stages of the experiment, completely disappeared.…”

“…The factor controlling this compensatory mechanism is the quantity of products of macrophage breakdown (PMB), which are produced by cytotoxic particles action and operate either directly (24), or through the activation of viable alveolar macrophage releasing a neutrophil attractant (25). It was shown, however, that in response to a fixed dose of the PMB the host might recruit into alveoli substantially different numbers of neutrophil leukocytes depending on its neurohormonal status (24,26,27).…”