The myofibroblast is an ultrastructurally and metabolically distinctiv
e connective tissue cell identified as a key participant in tissue rem
odeling in human granulation tissue, organ fibrosis, and the fibroblas
tic host response to malignant neoplasms. In this study of myofibrobla
sts in human lung diffuse alveolar damage (DAD), we identified 36 auto
psy cases in which DAD could be histologically documented. DAD is know
n to progress from initial injury through an exudative, proliferative,
and terminal fibrotic phase. In the exudative phase (16 cases), myofi
broblasts expressing alpha-smooth muscle actin (alpha-SMA) are found i
n the septa and less frequently in hyaline membranes. In the prolifera
tive phase (18 cases), many myofibroblasts in septa, hyaline membranes
, and intra-alveolar fibroplasia express alpha-SMA. The alpha-SMA phen
otype should be used in additional studies of myofibroblast differenti
ation, replication, and apoptosis, A better understanding of the biolo
gy of this cell type should offer new therapy for patients with DAD.