Alveolar Macrophages in a Particle "Overload" Condition

Abstract

ABSTRACT

Alveolar macrophage (AM)-mediated particle clearance from the lung via the conducting airways is an important mechanism by which relatively insoluble particles are translocated from the alveolar region. Diminution in the kinetics of removal of particles from the lung following the deposition of excessive particulate lung burdens (particle "overload"), which can be functionally viewed as the emergence of a sequestration compartment(s), suggests AM-related bases inasmuch as these cells are usually the primary reservoirs of deposited particles. Specific details about the mechanisms involved in AM-mediated lung clearance or about processes that may favor particle retention in the lung have not been well delineated. In the present investigation, the retention kinetics of a low to a relatively high lung burden of uniform polystyrene microspheres was examined with the highest burden studied resulting in a condition of particle "overload". We also assessed the lung's free cell response to these burdens over a prolonged period following the intrapulmonary deposition of the particles as we concurrently investigated particle-AM relationships during the alveolar clearance of the different lung burdens. Evidence obtained suggests the particles were gradually redistributed among members of the lung's free cell population of phagocytes during alveolar clearance. Additionally, polymorphonuclear leukocytes and blood monocyte-, pulmonary interstitial macrophage-like cells became increasingly prominent in the lung's free cell population over time during a condition of particle overload with the polystyrene microspheres; such findings suggest that these cells may potentially play a pathogenic role when lung burdens are excessive. Electron microscopic analyses suggested that aggregates of particle-laden macrophages, particle-containing Type I pneumocytes, and particle-containing pulmonary interstitial macrophages represent particle sequestration sites that contribute to diminished lung clearance during particle overload. However, our analyses of particle-AM relationships during particle overload point to AM with paniculate volume loads equal to or in excess of 60% of their normal volumes as being the main sequestrating compartment to which diminished rates of lung clearance can be virtually totally attributed. Moreover, the size of the AM-particle sequestering compartment appeared to remain stable over a 5 month period after the particles were deposited in the lungs. This latter observation suggests that once developed, the AM-particle sequestration compartment is essentially irreversibly maintained.