Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity.

Abstract

The adaptation of the alveolar phagocytosis response to the quantitative and qualitative features of dust deposited during inhalation consists not only in enhanced recruitment of alveolar macrophages (AM), but also in adding a more or less pronounced neutrophil leukocyte (NL) recruitment as an auxiliary participant of particle clearance. The NL contribution to clearance is especially typical for response to cytotoxic particles (quartz, in particular). An important feature of the adaptation considered is the limitation of the number of AM and NL recruited when an efficient clearance can be achieved by a lesser number ofceDls due to increased AM resistance to the damaging action of phagocytized particles. The main mechanism providing the adequacy of the alveolar phagocytosis response is its self-regulation through the products of macrophage breakdown (PMB). In a series of experiments with intraperitoneal and intratracheal injections of syngenetic PMB into rats and mice, it was shown that these products stimulate respiration and migration of phagocytic cells, their dose-dependent attraction to the site of PMB formation with the predominant NL contribution, increasing with the increase of amount of PMB, the AM and NL precursor cells recruitment from reserve pools, and the replenishment of these reserves in the process of hemopoiesis. At least some of the above effects are connected with the action of the lipid components of PMB. The action of specialized regulative systems of the organism can modify the response to PMB, judging by the results obtained by hydrocortisone injection. Autocontrol of alveolar phagocytosis requires great care in attempts at artificial stimulation ofthis process, as an excessive cell recruitment may promote the retention of particles in lungs.According to estimates based on comparison of calculated deposition of dust in miners' lungs with the actual amount found postmortem, about 98-99% of primarily deposited dust mass is cleared from the respiratory system (1). This impressive calculation allows us not only to explain why life is compatible

Some aspects of the problem of individual predisposition to silicosis.

“…A specific peculiarity of the silicosis development on the background of cold acclimatization is that, although the latter gave both indices of increased alveolar macrophage resistance to the cytotoxic effect of inhaled quartz particles (i.e., a decrese in both the degenerated AM percentage and the NL/AM ratio), the total cell count of bronchopulmonary lavage was significantly higher than in non-acclimatized rats under the same dust exposure. On the contrary, the decrease of this count is characteristic of other cases of attenuated cytotoxic effect and can be explained by a self-control mechanism mentioned previously (9,10). In rats not exposed to quartz, cold acclimatization had no influence on the bronchopulmonary cell population of lavage.…”

“…The damage to the macrophage results in a greater tendency for cytotoxic quartz dust to be retained in lungs and triggers compensatory mechanisms leading to a better pulmonary clearance (9,10). On the other hand, it is the same damage to macrophages, due to properties of silica particles not yet fully understood, that serves as a trigger mechanism for enhanced fibrogenesis (11,12) and possibly the immunopathologic components of silicosis.…”

“…For example, rats exposed to the same quartz dust inhalations vary significantly both in the percentage of degenerated alveolar macrophages in their bronchopulmonary lavages, and in the ratio of neutrophil leukocytes to alveolar macrophages; the latter being an indirect index of cytotoxic effect of the inhaled particle and is connected with the above percentage through a certain equation (9). On the other hand, group average values of both indices depend on the sex and age of rats exposed to dust.…”

“…For example, a change in the sensitivity of macrophages to the cytotoxicity of quartz particles may depend on sex (17), nutritional factors (9,30,31), muscular training (32,33), or longterm exposure to low levels of sulfur dioxide (34). The significance of this change for the development of silicosis is principally the same in all of these circumstances, irrespective of the factor's nature, although other interactive mechanisms may modulate for an end effect.…”

“…This proved to be correct in 94% of controls who had developed silicosis, and in 100% of those who had not. Listed in order of decreasing significance, the twelve factors are as follows: (1) type of underground job; (2) employment in a "dusty" industry before commencing work in the mine; (3) length of work period on the rock face; (4) housing conditions; (5) age when commencing work in a dusty environment; (6) presence of pre-existent chronic bronchitis; (7) possession of garden, kitchengarden, poultry, cow; (8) over-indulgence in alcohol; (9) smoking; (10) length of employment in the mine prior to the period of sharp decrease in dust levels; (11) past history of pneumonia; and (12) belonging to one of two main nationalities inhabiting the locality. In considering these factors, it should be stressed that, although significance of the latter feature is arbitrarily expressed as fifteen times less than that of the first, exclusion of any feature makes the prediction markedly less reliable.…”