Morphogenetic and functional activity of type II cells in early fetal rhesus monkey lungs

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Abstract
To evaluate further the role of type II alveolar epithelial cells in primate lung development, lungs of fetal (46 to 155 days gestational age [DGA]), postnatal, and adult rhesus monkeys were investigated with antibodies against surfactant protein A (SP‐A), Alcian blue (AB) staining, and periodic acid‐Schiff (PAS) staining with/without alpha‐amylase pre‐treatment. In adult and postnatal lungs, type II cells (cuboid shape; large, roundish nucleus) displayed a unique cytoplasmic staining for SP‐A. In prenatal lungs, a low‐columnar to cuboid type of cell with a large, roundish nucleus was first detectable by 62 DGA. It was the only cell type to line the distalmost tubules or buds of the prospective respiratory tract. It exhibited (initially partial) cytoplasmic staining for SP‐A. AB and PAS stainings showed the presence of acid glycoconjugates and large apical and/or basal glycogen fields. After 95 DGA, the lining of the distal respiratory tract additionally displayed flatter cells with immunoreactivity for SP‐A and non‐reactive zones. Columnar epithelium (pseudostratified or simple) never stained for SP‐A. We conclude that morphologically identifiable type II cells first appear in fetal rhesus monkey lungs by 62 DGA (pseudoglandular period). The cells may already synthesize surfactant and extracellular matrix components. They generate type I cells, and thus the entire pulmonary acinus lining. These conclusions for the rhesus monkey fully agree with our earlier conclusions for another primate, the human, and for rodents. However, as presently shown, primates differ greatly from rodents with respect to the timing of type II cell differentiation (at 29–38% versus 73–75% of gestation or at 22–25% versus 48–49% of prenatal lung development).