Composition of the pulmonary interstitium during normal development of thehuman fetus

Normal lung development is dependent on epithelial-mesenchymal interactions . This study was undertaken to examine the structure of the interstitium of the developing human fetal lung, concentrating particularly on the first a nd second trimesters. Lung tissue was obtained at autopsy from nonmalformed , nonmacerated cases of spontaneous abortion (n = 15), stillbirth (n = 9), and very early neonatal death (n = 5) (range of gestations, 10-42 weeks). P araffin-embedded tissue sections were examined using immunohistochemical me thods to determine expression of collagens I, III, IV, V, and VI; the glyco proteins fibronectin and laminin; and the intermediate filaments vimentin, alpha-smooth muscle actin (alpha SMA), and desmin. Collagens III and VI and cells expressing alpha SMA were present consistently at points of airway b ranching and secondary crest formation, indicating a role for these compone nts in the initiation and stabilization of airway branches in the developin g lung. Desmin expression by stromal cells succeeded alpha SMA temporally a nd may represent a marker of terminal smooth muscle differentiation within the airway; it was not detected in the vascular tree. Other components were widely expressed throughout the extracellular matrix, including basement m embranes, at all gestations. The spatial and temporal patterns of expressio n of components of the lung interstitium provide clues to the mechanisms un derlying normal human lung development and possible insights into the patho genesis of fetal and neonatal lung disease.