Human pulmonary acinar aplasia: Reduction of transforming growth factor-beta ligands and receptors

Pulmonary hypoplasia has been found in the human neonatal autopsy populatio n and has been attributed to an alteration in epithelial-mesenchymal intera ctions during development of the lung. Pulmonary acinar aplasia is a very r are and severe form of pulmonary hypoplasia. The transforming growth factor -betas (TGF-beta) are multifunctional regulatory peptides that are secreted by a variety of normal and malignant cells and are expressed in developing organs including the lung; their tissue distribution patterns have possibl e significance for signaling roles in many epithelial-mesenchymal interacti ons. Here, we report our examination of TGF-beta in the lungs of a term fem ale infant diagnosed with pulmonary acinar aplasia whose autopsy revealed e xtremely hypoplastic lungs with complete absence of alveolar ducts and alve oli. Immunohistochemical and in situ hybridization analyses were used to lo calize and measure the proteins and mRNA, respectively, for TGF-beta 1, TGF -beta 2, TGF-beta 3, and TGF-beta type I and type II receptors (TGF-beta RI and RII) in formalin-fixed and paraffin-embedded sections of these hypopla stic lungs and normal lungs. Immunostaining for TGF-beta 1,TGF-beta 2, and TGF-beta RI and RII was significantly lower in the bronchial epithelium and muscle of the hypoplastic lungs than in normal lungs, whereas no differenc e was detected in staining for other proteins including Clara cell 10-kD pr otein, adrenomedullin, hepatocyte growth factor/scatter factor, and hepatoc yte growth factor receptor/Met in the hypoplastic and normal lungs or in th e liver and kidneys of this infant compared with normal liver and kidney. I n addition, in situ hybridization showed that TGF-beta 1 and TGF-beta RI tr anscripts were considerably reduced in the bronchial epithelium of the hypo plastic lung compared with normal lung. These results show that there is a selective reduction of TGF-beta in pulmonary acinar aplasia and suggest tha t the signaling action of TGF-beta in epithelial-mesenchymal interactions i n the lungs of this developmental condition may be compromised.