Small-granule APUD cells in relation to airway branching and growth: a quantitative, cartographic study in Syrian...

Small-granule APUD cell clusters and their clear-cell precursors were mapped in serial 2-micron glycol methacrylate-embedded, periodic acid-Schiff (PAS)-lead hematoxylin-stained sections of 13-, 14-, and 15-day fetal hamster lungs. Every sixth section was drawn from a camera lucida projection on tracing paper. Each tracing included the profiles of nonalveolated air passages and the locations of small-granule cell clusters and solitary clear cells. Airways containing ciliated cells and those surrounded by condensed mesoderm were also labeled. Single clear cells were rare in fetal hamster lung. Of 2,368 endocrine cell loci identified in the three fetal age groups examined, only 14 were single clear cells. A preliminary survey of the entire left and right lungs showed that the pattern of airway and small-granule cell development in the infracardiac lobe was similar to that occurring in the remainder of the lung; this lobe was accordingly considered a model for the whole lung, and the ontogeny of its small-granule cell population was quantitated and compared with results of similar quantitative mapping of this lobe in an adult animal (Hoyt et al., 1982a,b). Along the lobar bronchus of the 13-day infracardiac lobe and proximal portions of its main branches, small-granule cell clusters occurred most often near airway intersections. As the number and density increased in subsequent fetal stages, small-granule cell clusters became conspicuous along internodal bronchial segments. In distributing bronchioles, the population density of small-granule cell clusters decreased between 13 and 14 days but more than doubled by day 15. Unlike human lungs, where centrifugally developing small-granule cell clusters are firmly established in terminal bronchioles well before birth, most peripheral bronchioles in fetal hamster were devoid of small-granule cell clusters, even at 15 days, one day before birth. Comparison of numerical population densities in this lobe of fetal and adult lungs indicates that small-granule cell clusters continue to form past day 15 and suggests that they are considerably more numerous in adult than fetal lung.