Possible mechanisms to explain dust overloading of the lungs

Dietary microparticles implicated in Crohn’s disease can impair macrophage phagocytic activity and act as adjuvants in the presence of bacterial stimuli

“…Microparticles impaired the accumulation of phagocytosed beads, with a sharp decrease in the number of macrophages accumulating 4+ latex beads. These results suggested that dietary microparticle uptake decreased the phagocytic capacity of macrophages rather than affecting the process of phagocytosis itself and is consistent with the 'particle overload' hypothesis proposed by Morrow et al to explain the toxicity of inhaled particles [37]. Studies using alveolar macrophages found that when the phagocytosed particle burden occupied ~6 % of the internal cell volume, clearance mechanisms were impaired and completely blocked when the burden reached ~60 % [38,39].…”

Elemental Carbon-Based Method for Monitoring Occupational Exposures to Particulate Diesel Exhaust

“…Under these circumstances, dose and mechanistic factors could be important in the estimation of human risk because the dose to which humans are exposed may be below a threshold level required for carcinogenesis or the mechanisms responsible for tumor formation in rodents may not occur in humans (Cohen and Ellwein, 1992). The high diesel particulate concentrations to which rats were exposed are thought to effect a "lung overload" (Morrow, 1988) response involving inflammation and cell proliferation (Mauderly et al, 1992(Mauderly et al, , 1994. This response, which is induced by the insoluble carbon core of the diesel particle, has been proposed as the dominant factor in carcinogenesis in rats, and reportedly may be required for tumor formation (Pepelko and Chen, 1993).…”

Small difference in carcinogenic potency between GBP nanomaterials and GBP micromaterials

“…The hypothesis was expressed that GBP material induced lung carcinogenicity in the rat is only due to excessive particulate lung burdens, and the term ''lung overload'' was generated to describe these conditions (Morrow 1988(Morrow , 1992. The theory is that in the particle-overloaded lung, an impairment of alveolar macrophage-mediated lung clearance leads to accumulation of high lung dusts burdens, which is associated with inflammation.…”