Theodore N. Finley

Defective Lung Macrophages in Pulmonary Alveolar Proteinosis

Lung macrophages obtained by segmental lavage from three patients with pulmonary alveolar proteinosis were studied in vitro. The macrophages exhibited morphologic abnormalities including excessive lipid accumulation and giant secondary lysosome formation. These cells survived poorly in tissue culture, showed impaired chemotactic activity, and had decreased adhesiveness to glass. They phagocytized normally but had substantially decreased capacity to kill ingested Candida pseudotropicalis. Evidence was obtained that the macrophage defect was acquired and probably related to ingestion of the proteinaceous alveolar fluid. Peripheral blood monocyte function was normal in one patient and morphologic abnormalities were produced in normal monocyte-derived macrophages cultured with proteinaceous lavage material. These studies suggest that the lung macrophage in alveolar proteinosis is a defective cell as a consequence of an abnormal pulmonary environment.

Comparison of the composition and surface activity of “alveolar” and whole lung lipids in the dog

Abstract 1. 1.The surface activity of lung extracts has been shown to be due to a lipoprotein complex which lines the alveolar surface. The lipids responsible for this surface activity were studied by endobronchial lavage of dog lung in vivo . Lipids obtained from the alveolar surface by lavage were identified and compared with those obtained from an homogenate of whole lung. 2. 2.The lipids obtained by lung lavage comprise only a very small proportion of total lung lipids and differ from the latter in several important respects. The predominant lipid from both sources is lecithin (55% of “alveolar” lipids but only 41% of whole lung lipids). “Alveolar” lecithin contained 66% esterified palmitate; whole lung lecithin contained only 39%. Total saturated fatty acids were also much higher in “alveolar” lecithin. 3. 3.Lecithin monolayers from lung lavage lowered surface tension to 0.5 dynes/ cm whereas whole lung lecithin produced a minimum tension of only 20 dynes/cm. Only one other lipid component consistently produced marked surface-tension lowering. This component, a phospholipid, was about 6% of both alveolar and whole lung total lipids. 4. 4.This surface active phospholipid was shown to be phosphatidyl- N , N -dime-thylethanolamine containing 59–62% esterified palmitate with a distribution of total fatty acids very similar to that of “alveolar” lecithin. It is suggested that dipalmitoyllecithin, the principal pulmonary surface active agent, is formed in lung by conversion of phosphatidylethanolamine to lecithin by way of phosphatidyldimethylethanolamine.

Alterations in pulmonary surface active lipids during exposure to increased oxygen tension.

Extracts of normal lung have been shown to contain a surface active agent that by decreasing alveolar surface tension serves to stabilize the alveoli during respiration (1-3). This surfactant has been shown to contain lipid probably complexed with protein (4, 5). Several investigators have suggested that the lipid is primarily dipalmitoyl lecithin [L-a-(dipalmitoyl) glycerophosphoryl choline], a highly surface active phospholipid (5-7). Increased surface tension in lung extracts occurs in certain disease states associated with respiratory distress (2). In man these states include the respiratory distress syndrome of infancy and oxygen toxicity. A similar respiratory distress syndrome can be produced experimentally in dogs and rabbits by exposure to increased oxygen tension. In both clinical and experimental situations respiratory distress, pulmonary edema, and atelectasis are associated with increased pulmonary surface tension (8-10). Our purpose in the present experiment was to induce changes in pulmonary surface tension in dogs by exposure to increased oxygen tension, to remove pulmonary surfactant by endobronchial lavage, and to measure lipid composition and surface activity. Endobronchial lavage rather than lung mincing was utilized to obtain alveolar surface lipids free of whole lung lipids, since previous studies had shown that whole lung lipids differ markedly from those of the alveolar surface (11).

Alterations in Pulmonary Morphology and Surface Activity During Experimental Oxygen Toxicity.

Excerpt Increased oxygen tension as therapy for respiratory failure is frequently encountered clinically. A syndrome of progressive respiratory distress, pulmonary edema, and increased surface tens...