The alveolar macrophage

The alveolar macrophage is one of the few tissue macrophage populations readily accessible to study both in the human and in animals. Since harvesting of these cells by bronchoalveolar lavage was first described in 1961, alveolar macrophages have been extensively investigated. This population is the predominant cell type within the alveolus, and undoubtedly serves as the first line of host defense against inhaled organisms and soluble and particulate molecules. Early studies focussed on this endocytic role and delineated the cells' phagocytic and microbicidal capacities. More recent investigations demonstrated an extensive synthetic and secretory repertoire including lysozyme, neutral proteases, acid hydrolases and O2 metabolites. In addition, the complex immunoregulatory role of the macrophage has also been appreciated. These cells have been shown to produce a wide variety of pro- and anti-inflammatory agents including arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathways, cytokines which modulate lymphocyte function and factors which promote fibroblast migration and replication.     

Breath-by-breath alveolar gas exchange

A method is described for breath-by-breath measurement of alveolar gas exchange corrected for changes of lung gas stores. In practice, the subject inspires from a spirometer, and each expired tidal volume is collected into a rubber bag placed inside a rigid box connected to the same spirometer. During the inspiration following any given expiration the bag is emptied by a vacuum pump. A computer monitors inspiratory and expiratory tidal volumes, drives four solenoid valves allowing appropriate operation of the system, and memorizes end-tidal gas fractions as well as mixed expired gas composition analyzed by mass spectrometer. Thus all variables for calculating alveolar gas exchange, based on the theory developed by Auchincloss et al. (J. Appl. Physiol. 21: 810-818, 1966), are obtained on a single-breath basis. Mean resting and steady-state exercise gas exchange data are equal to those obtained by conventional open-circuit measurements. Breathing rates up to 30 X min-1 can be followed. The breath-to-breath variability of O2 uptake at the alveolar level is less (25-35%) than that measured at the mouth as the difference between the inspired and expired volumes, both at rest and during exercise up to 0.7 of maximum O2 consumption.     

Estrogen receptor regulation of pulmonary alveolar dimensions: alveolar sexual dimorphism in mice

Female rats and mice have smaller and, per body mass (BM), more alveoli and alveolar surface area (Sa) than males of their respective species. This sexual dimorphism becomes apparent about the time of sexual maturity. It is prevented in rats (not tested in mice) by ovariectomy at age 3 wk. In female mice, estrogen receptor (ER)-alpha and ER-beta are required for formation of alveoli of appropriate size and number. We now report the average volume of an alveolus (va) and the number of alveoli per body mass (Na/BM) were not statistically different between ER-alpha(-/-) and wild type (wt) males. However, the combination of a larger value for va and a smaller value for Na/BM, though neither parameter achieved a statistically significant intergroup difference, resulted in a statistically significant lower Sa/BM in ER-alpha(-/-) males compared with wt males. In ER-beta(-/-) males, va was bigger and Na/BM and Sa/BM were lower compared with wt males. Wt males had larger alveoli and lower Na/BM and Sa/BM than wt females. The wt sexual dimorphism of va, Na/BM, and Sa/BM was absent in ER-alpha(-/-) mice. Alveolar size did not differ between ER-beta(-/-) females and males but Na/BM and Sa/BM were greater in ER-beta(-/-) females than in ER-beta(-/-) males. The results in male mice, with prior findings in female mice, 1) demonstrate estrogen receptors have a smaller effect on alveolar dimensions in male than female mice, 2) show ER-alpha and ER-beta are required for the sexual dimorphism of alveolar size, and 3) show ER-alpha is needed for the sexual dimorphism of body mass-specific alveolar number and surface area.     

A continuous alveolar macrophage cell line: Comparisons with freshly derived alveolar macrophages

Summary Responses of a recently developed rat alveolar macrophage cell (NR8383.1) line were compared to those of freshly derived alveolar macrophages in vitro. Marked inter- and intraspecies heterogeneity in levels of phagocytosis of unopsonizedPseudomonas aeruginosa or zymosan was noted among freshly derived alveolar macrophages from rats, rabbits, and baboons. In contrast, phagocytic responses of alveolar macrophage cell line were predictable and highly reproducible. Similar results were obtained in measuring oxidative burst, as indicated by the production of H₂O₂ and luminol-enhanced chemiluminescence. Responses were again highly variable in freshly derived alveolar macrophages stimulated with zymosan or phorbol myristic acetate; moreover, freshly derived alveolar macrophages exhibited a wide range of chemiluminescence activity in unstimulated cultures. Results strongly suggest that data derived from the continuous alveolar macrophage culture NR8383.1 can be extrapolated to freshly derived alveolar macrophages of various species, and in many experiments will be useful in avoiding the significant animal-to-animal variance observed among freshly derived cell preparations. This work was supported in part by grant A119811 and SCOR HL23578, from the National Institutes of Health, Bethesda, MD. Portions of these studies appeared as a poster presentation at the American Society for Microbiology, Atlanta, GA, 1987.     

Enhanced glycolysis-mediated energy production in alveolar stem cells is required for alveolar regeneration

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Carousel effect in alveolar models

Experimental work over the past decade has shown that recirculation in alveoli substantially increases the transport of particles. We have previously shown that, for nondiffusing passive particles, this can be understood with the aid of Moffatt's famous corner flow model. Without wall motion, passive particles recirculate in a regular fashion and no chaos exists; however, wall motion produces extensive chaotic flow. Aerosols typically do not follow this flow as they are fundamentally different from fluid particles. Here, we construct a simple model to study diffusing particles in the presence of recirculation. We assume that all particles are passive, that is to say that they do not significantly alter the underlying flow. In particular, we consider particles with high Peclet number and neglect inertial effects. We modify the Lagrangian system for corner eddies to accommodate diffusing particles. Particle transport is governed by Langevin equations. Ensembles of diffusing particles are tracked by numerical integration. We show that transport of diffusing particles is enhanced by sufficiently strong underlying recirculation through a mechanism that we call the "carousel effect." However, as the corner is approached, the recirculation rapidly decreases in intensity, favoring motion by diffusion. Far from the corner's apex, recirculation dominates. For real alveoli, the model indicates that sufficiently strong recirculation can enhance transport of diffusing particles through the carousel effect.