LOSS OF EDB-CELLS IN HUMAN FETAL LUNG( FIBRONECTIN ISOFORM IS ASSOCIATED WITH DIFFERENTIATION OF ALVEOLAR EPITHELIAL)

Cell-matrix interactions have been shown to regulate the development o f the lung, particularly airway branching and alveolarization. Fibrone ctin is the major constituent of pulmonary extracellular matrix and ex ists in multiple isoforms arising from alternative RNA splicing. EDA a nd EDB are the two major alternatively spliced segments, the expressio n of which is regulated in a spatiotemporal and oncodevelopmental mann er, In this study, we investigated immunohistochemically the distribut ion of the EDA- and EDB-containing fibronectin isoforms (referred to a s EDA fibronectin and EDB+ fibronectin, respectively) in normal and hy poplastic human lungs at different gestational ages to explore the rol e of these fibronectin isoforms in alveolarization. EDA(+) fibronectin was expressed around the distal airspaces throughout the development of both normal and hypoplastic lungs, In contrast, the expression of E DB+ fibronectin was restricted to the lung with morphologically immatu re acinar complex, typically observed in normally developing lungs of <30 gestational weeks or in hypoplastic lungs, To further confirm the restricted expression of EDB+ fibronectin in immature acinar complex, me examined the correlation of EDB+ fibronectin expression with that o f the surfactant protein SP-A, a biochemical marker for the differenti ated type II pneumocytes. A clear inverse relationship between the imm unoreactivities for EDB+ fibronectin and SP-A was observed in both con trol and hypoplastic lungs, Given the proposed importance of fibronect ins in the differentiation of alveolar epithelial cells, our results s uggest that the EDB segment plays a regulatory role in the differentia tion of immature acinar epithelial cells into type II pneumocytes, The EDB segment may also serve as a new histochemical marker for the func tional maturity of fetal lung tissues.