Pulmonary lymphangioleiomyomatosis (LAM), a disease of young women of child-bearing age and is characterized by the proliferation of abnormal smooth muscle cells (LAM cells) in the pulmonary interstitium and by progressive destruction of pulmonary tissue, leading to the widespread formation of pulmonary parenchymal cysts. In collaboration with the Pulmonary-Critical Care Medicine Branch (Dr. J. Moss and colleagues) and the Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, D.C., we have undertaken extensive studies of the pathology of LAM with special emphasis on the application of immunohistochemical techniques for multiple antibody labeling as well as methods of transmission and scanning electron microscopy. These studies have lead to the following conclusions:1) The LAM cells are morphologically heterogeneous and form nodules in which they show different degrees of differentiation.2) In these nodules, the spindle-shaped LAM cells tend to occupy the central regions, whereas the more differentiated epithelioid cells are distributed along the periphery.3) Most LAM cells, regardless of morphology, express matrix metalloproteinase -2 (MMP-2, the 72-kDa gelatinase A, which is capable of hydrolyzing elastin and the fibrillar collagens) and smooth muscle actin.4) The spindle-shaped LAM cells have a greater proliferative capacity and a more abundant content of membrane type-1-MMP (MT-1-MMP; an enzyme that is needed to activate MMP-2), than do the epithelioid LAM cells.5) Estrogen and progesterone receptors are downregulated in lung tissue obtained after prolonged hormonal treatment of LAM.6) Increased activity and activation of MMPs appear to be major factors contributing to the connective tissue destruction that mediates the formation of the pulmonary parenchymal cysts in LAM.7) Epithelioid LAM cells show evidence of partial melanogenesis. 8) The proliferation of LAM cells is associated with hyperplasia of type II alveolar epithelial cells. - lung, lymphangioleiomyomatosis, immunohistochemistry, apoptosis, Bcl-2, Bax
