INTRACYTOPLASMATIC CRYSTALLOID INCLUSIONS IN ALVEOLAR MACROPHAGES IN ANIMAL MODELS OF EMPHYSEMA

We described the occurrence of crystalloid inclusions in alveolar macrophages of pallid mice with genetic emphysema at the time of septal disruption. Using an immunogold technique these inclusions were identified as collagen-derived products. In the present study we investigated the presence of similar features in alveolar macrophages in C57BL/6J mice instilled intratracheally with µg 25 of leukocyte elastase, tight-skin and blotchy mice, which develop spontaneous emphysema, at times when septal destruction is known to occur. The cristalloid inclusion were never observed in alveolar macrophages from C57BL/6J mice 14-21 days after elastase treatment. A small number of inclusions were found in few alveolar macrophages of 1-2 month-old tight-skin mice which develop massive emphysema very early in life. On the contrary, several macrophages of blotchy mice of 3-4 months of age exhibited a constant number of crystalloid inclusions. Although the mechanism for the formation of the crystalloid inclusion is not known, the degree of the protease burden in the alveolar septa as well as the time required for the development of emphysema appear to be of importance. The inclusions are a characteristic feature in alveolar macrophages of mice with slow developing emphysema and with a low (blotchy) or moderate (pallid ) amount protease burden on alveolar septa. While this feature is not relevant in macrophages of mice in which emphysema develops rapidly and is associated with a marked increase in alveolar septa protease burden (C57BL/6J after i.tr. elastase, and tight-skin mice). The different way of collagen degradation (intracellular or extracellular) may influence the remodeling of interstitial matrix after an alveolar injury.