Development of macrophages in the lungs of fetal rabbits, rats, and hamsters

Fetal rabbits (days 13-32), rats (days 14-22), and hamsters (days 11-15) and selected postnatal animals were examined for pulmonary macrophages or their precursors in 2-micron sections stained by PAS-lead hematoxylin (all species), electron micrographs (rabbit and rat), and cytochemical incubations for acid phosphatase (rabbit and rat), aliesterase, and N-acetyl glucosaminidase (rabbits). All methods revealed macrophages in perinatal specimens. The appearance and distribution of these cells were compared in the different preparations to establish the reliability of PAS-lead hematoxylin for identifying them in less developed fetal lungs, where they are less active for lysosomal enzymes the earlier the stage examined. In the sections, macrophages are seen to possess a round or indented nucleus, an irregular contour, and a deep purplish-gray cytoplasm containing a variety of pink PAS-stained granules, equated with heterolysosomes by ultrastructural cytochemistry. In less developed lungs, macrophages occur along with putative precursors having a more rounded outline and fewer PAS-stained granules. In pseudoglandular lungs these precursors predominate over rather vacuolated macrophages resembling Hofbauer cells. In all three species both cell types first appear in the stroma during the bronchial bud stage and are frequently seen to divide from that time on. The earliest precursors have a relatively sparse cytoplasm which later increases in daughter cells. Hofbauer-like cells disappear during the canalicular stage of development, replaced by macrophages and transitional forms from the more rounded precursors. In day 21 rabbit lungs, scattered stromal cells are reactive for aliesterase, and, some days later, for acid phosphatase and glucosaminidase. Free mononuclear cells are rare in airways of pseudoglandular lungs but become common later. A day or two before birth in rats, free cells range between rather undifferentiated leukocytes to typical macrophages, but cells with the macrophage's complete repertory of inclusions are seen only after birth. In the fetus, typical monocytes were not identified in either the pulmonary stroma or the airways. A replicating population of macrophage-like cells therefore resides in fetal lungs. It is established before bone marrow is formed and, in rats, before monocytes have appeared in the circulation.