Author/Authors :
M. P. Bernardin، نويسنده , , B. E. Lehnert، نويسنده ,
Abstract :
A model of particle-alveolar macrophage relationships during alveolar-phase clearance of a low burden of insoluble particles from the ratʹs lung is developed. Model development begins with transport of particle-containing alveolar macrophages (AM) out of the alveoli via the tracheobronchial route as the only operative clearance mechanism, and it advances with the inclusion of AM proliferation, and AM autolysis and the rephagocytosis of freed particles as additional operative mechanisms. At each stage of development, simulated results are compared with data obtained from a previous study of AM during the alveolar clearance of a low burden of insoluble polystyrene microspheres (Lehnert et al. (1989) Am. J. Respir. Cell Mol. Biol. 1, 145–154). We find that: (1) the transport of the particle-containing AM from the lungs is consistent with a transport mechanism that is time-dependent, characterized by more rapid AM removal at earlier times and slower AM removal at later post-depositional times, (2) AM proliferation with allocations of particles to progeny cells is an absolutely vital component to the model, which, along with tracheobronchial transport, forms the basis or zeroth-order portion of the model, and (3) for times well after the post-particle depositional period, AM autolysis and the rephagocytosis of freed particles are first-order type physiological mechanisms that act to refine simulations of the particle-AM relationship data. Overall, our final model predictions are shown to be in close agreement with the actual experimental data. The model supports an AM removal rate that varies continuously from an initial value of 3.0% of the resident population per day to a final value of 0.35% of the AM population per day, and an AM proliferation rate of 0.85% per day. These values for both the transport-rate range and the AM proliferation rate are consistent with previously reported values.
