Apoptosis and lung injury.
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.
Lu
Qing
Q
Pulmonary Vascular Research Laboratory, Providence Veterans Affairs Medical Center, Department of Medicine Brown Medical School, Providence, RI 02908, USA.
Harrington
Elizabeth O
EO
Rounds
Sharon
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology*; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*