Phenotypic modulation of alveolar myofibroblasts in transplanted human lungs

We examined 33 successive pulmonary biopsy specimens from nine patients who underwent pulmonary transplantation; they were compared to "normal" lung tissue selected from routine transbronchial biopsy material and also to surgical biopsy specimens from a previously reported study. We used as controls the three successive biopsy specimens from Patient 7, in whom rejection reaction did not develop, and the two specimens from Patient 6, who had pneumonia caused by cytomegalovirus. The material was embedded in paraffin, and the sections were stained by hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, and Gomori's silver stains. They were also immunostained for alpha-smooth muscle actin (alpha-SMA), desmin, transforming growth factor beta1, tumor necrosis factor alpha, keratin, CD3, CD20, CD68, and HLA-dr. In all of the lung tissue from patients in whom a rejection reaction developed, alveolar myofibroblasts (MFs) expressed alpha-SMA. Sometimes, alpha-SMA expression appeared before the classical manifestations of rejection reaction. MFs labeled by alpha-SMA antibody did not express desmin; alveolar septa containing alpha-SMA-positive cells were frequently lined by transforming growth factor beta1 and, occasionally, tumor necrosis factor alpha-laden Type II pneumocytes. In lung tissue (from successive biopsies) that did not show evidence of rejection reaction, alveolar MFs did not express alpha-SMA. Our findings demonstrate that modulation of alveolar MFs is one of the manifestations of rejection in transplanted lungs; furthermore, they suggest that alpha-SMA staining might be useful in predicting rejection reaction before the classical cellular events occur.