Apoptosis is important in developmental biology and in remodeling of tissues during repair.
Apoptosis also plays important roles in the progression of many diseases. The cellular and molecular
mechanisms of apoptosis, in general, have been extensively demonstrated. However, the causes and the
roles of apoptosis of various cell types in the lung are not well understood. We have determined that
adenosine/homocysteine causes lung vascular endothelial cell apoptosis by inhibition of carboxyl
methylation of the small GTPase, Ras, through inhibition of isoprenylcysteine carboxyl methyltransferase
(ICMT) activity, leading to inactivation of Ras and the subsequent disruption of focal
adhesion complexes, resulting in cell-extracellular matrix detachment and anoikis. Apoptosis can either
ameliorate or exacerbate lung injury, depending upon the cell type. Although apoptosis of polymorphonuclear
leukocytes in the lung prevents inflammation and the development of acute respiratory
distress syndrome during acute lung injury, Fas/FasL-mediated alveolar epithelial cell apoptosis promotes
acute lung injury and pulmonary fibrosis. Lung epithelial and endothelial cell apoptosis also
contributes to the development of emphysema. This article focuses on elucidating the mechanisms of
adenosine/homocysteine-induced endothelial cell apoptosis. We also review the current understanding
of the role of lung cell apoptosis in acute lung injury, pulmonary fibrosis and emphysema. |