| Title |
| Free Radical Protection from and Exacerbation of Lung Injury |
| Description |
| Dr. Matalon’s research interests also focus on the role of free radicals as protective agents and as mediators of tissue injury, specifically in the context of the alveolar epithelium. Currently, two approaches are being pursued. The first is an investigation of the role of reactive oxygen-nitrogen intermediates in the killing of Mycoplasma pneumoniae. These mycoplasmas account for 20 to 30 percent of all pneumonias in humans, and exacerbate the pathophysiology of asthma, chronic obstructive disease and other pulmonary diseases. Man is the only host of M. pneumoniae, but M. pulmonis infection in mice provides an excellent animal model that reproduces the essential features of human disease. Moreover, C3H/He mice are susceptible but C57BL/6 mice are resistant. Presently, the basic mechanisms by which some hosts, but not others, kill mycoplasmas in vivo have not been elucidated. Dr. Matalon and colleagues have hypothesizes that in the early stages of infection, mycoplasmas are killed by reactive oxygen-nitrogen intermediates (ROS) produced by activated alveolar macrophages (AM). Surfactant protein A (SP-A) is essential and necessary or this killing to occur by (i) upregulating production of nitric oxide by activated AM, and (ii) stimulating phagocytosis of mycoplasmas by AM. Furthermore, injury to SP-A by reactive oxygen-nitrogen species abrogates its host-defense functions. This hypothesis is being tested in vitro, using AM isolated from the lungs of these mice, and in vivo using congenic germ-free knock-out mice. The second series of studies involves analysis of hyeroxic injury. Active sodium (Na+) transport across the adult alveolar epithelium plays an important role in the maintenance of lung fluid balance, especially after sublethal hyperoxic injury to the blood-gas barrier, when the effectiveness of the passive Starling forces is diminished. Presently, the mechanisms by which Na+ ions enter the apical membranes of normal and oxygen-injured alveolar epithelial cells, have not been elucidated. Based on preliminary data, Dr. Matalon and colleagues hypothesize that alveolar type II cells (ATII) contain Na+ channels with low affinity to amiloride and that the properties and spatial distribution of these channels may be altered by exposure to sublethal hyperoxia. Since sodium channels conduct at rates far exceeding that of any other transporter, and their activities may be upregulated by a number of agents, they may form a major pathway for the entry of Na+ ions into alveolar epithelial cells. |
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