Alveolar clearance macrophages

Stober W, Morrow PE, Koch W et al. 1994. Alveolar clearance and retention of inhaled insoluble particles in rats simulated by a model inferring macrophage particle load distributions. J Aerosol Sci 25 975-1002. 

Clearance of foreign materials (particles) from the lung and airways depends on the function of macrophages, ciliated cells and secretory cells, and on the physical and chemical properties of the alveolar cells. All these are affected by ozone exposure. Single acute exposure of animals and humans to ozone concentrations less than 0.6 ppm have been shown to accelerate clearance of particles from the tracheobronchial tree whereas acute exposures to ozone levels greater than 0.6 ppm caused a delay in particles clearance [79, 261]. Repeated exposures (2 h daily for 14 days) to 0.1 ppm ozone gave rise to acceleration in alveolar clearance of latex particles but had no effect on tracheobronchial clearance. These results, related to morphological studies, are consistent with certain adaptation [278-283]. 

Lehnert BE, Morrow PE. Association of 59-iron oxide with alveolar macrophages during alveolar clearance. Exp Lung Res 1985 9 1-16. 

Lehnert BE, Ortiz JB, London JE, Valdez YE, Cline AJ, Sebring RJ, Tietjen GL. Migratory behaviors of alveolar macrophages during alveolar clearance of light and heavy burdens of particles. Exp Lung Res 1990 16 451-479. 

From a drug delivery perspective, the components of the host defence system comprise barriers that must be overcome to ensure efficient drug deposition as well as retention in and absorption from the respiratory tract. Important non-absorptive clearance mechanisms include mucociliary clearance, alveolar macrophages and metabolism (Figure 6.2). 

If the site of injury or deposition is the alveoli, alveolar maerophages (AM) scavenge and ingest the foreign particulate matter, serving anti-infection and clearance functions. Macrophages have a life span averaging 60 days and... 

Barriers to pulmonary absorption of proteins and peptides include respiratory mucus, mucociliary clearance, pulmonary enzymes/proteases, alveolar lining layer, alveolar epithelium, basement membrane, macrophages and other cells [3, 18]. The molecular weight cutoff of tight junctions for alveolar type I cells is 0.6 nm, while endothelial junctions allow the passage of larger molecules (4-6 nm). In order to reach the bloodstream in the endothelial vasculature, proteins and peptides must cross this alveolar epithelium, the capillary endothelium, and the intervening extracellular matrix. 

Rolls, J. K., Lei, D., Nelson, S., Summer, W. R. and Shellito, J. E. (1997). Pulmonary cytokine gene therapy. Adenoviral-mediated murine interferon gene transfer compartmentally activates alveolar macrophages and enhances bacterial clearance. Chest 111, 104S. 

Lung infections with viruses suppress the bacterial clearing activity of the lung by impairing alveolar macrophage function and mucocihary clearance, thus setting the stage for secondary bacterial pneumonia. 

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