Alveolar proteinosis and phospholipidoses of the lungs.
Three pulmonary disease conditions result from the accumulation of phospholipids in the lung. These conditions are the human lung disease known as pulmonary alveolar proteinosis, the lipoproteinosis that arises in the lungs of rats during acute silicosis, and the phospholipidoses induced by numerous cationic amphiphilic therapeutic agents. In this paper, the status of phospholipid metabolism in the lungs during the process of each of these lung conditions has been reviewed and possible mechanisms for their establishment are discussed. Pulmonary alveolar proteinosis is characterized by the accumulation of tubular myelin-like multilamellated structures in the alveoli and distal airways of patients. These structures appear to be formed by a process of spontaneous assembly involving surfactant protein A and surfactant phospholipids. Structures similar to tubular myelin-like multilamellated structures can be seen in the alveoli of rats during acute silicosis and, as with the human condition, both surfactant protein A and surfactant phospholipids accumulate in the alveoli. Excessive accumulation of surfactant protein A and surfactant phospholipids in the alveoli could arise from their overproduction and hypersecretion by a subpopulation of Type II cells that are activated by silica, and possibly other agents. Phospholipidoses caused by cationic amphiphilic therapeutic agents arise as a result of their inhibition of phospholipid catabolism. Inhibition of phospholipases results in the accumulation of phospholipids in the cytoplasm of alveolar macrophages and other cells. While inhibition of phospholipases by these agents undoubtedly occurs, there are many anomalous features, such as the accumulation of extracellular phospholipids and surfactant protein A, that cannot be accounted for by this simplistic hypothesis.
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Biochemical Pathology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
D000818:Animals; D006801:Humans; D008064:Lipidoses / Q000209:etiology*; D008074:Lipoproteins / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity
D008074:Lipoproteins; D010743:Phospholipids; D011506:Proteins; D011663:Pulmonary Surfactants; D012822:Silicon Dioxide