A B S T R A C T Evidence for the presence of peroxidative metabolism in rabbit alveolar macrophages (AM) has been obtained from the following observations: (a) catalase is present in high concentrations; (b) peroxidase activity could not be detected employing guaiacol as substrate; (c) the irreversible inhibition of AM catalase by aminotriazole served as a detection system for H202 and demonstrated increased intracellular H202 after phagocytosis; (d) formate oxidation, a marker of catalase-dependent peroxidations, occurs in resting AM and is increased by phagocytosis; (e) measurements of H202 accumulation in a dialysate of AM demonstrated twofold increase during phagocytosis; and (f) aminotriazole diminishes 02 utilization and '4CO2 production from labelled glucose and pyruvate. It is concluded that, while catalase-dependent H202 metabolism is not essential for particle entry, this pathway represents one of the metabolic pathways stimulated by particle entry in the AM. INTRODUCTIONThe alveolar macrophage (AM) plays an important role in pulmonary bacterial clearance by functioning as a phagocyte. While phagocytosis by the AM requires oxygen and stimulates both 02 consumption (Qo2) and 14CO2 production from labeled glucose (2), the relation of these metabolic pathways to H202 has not been de-
In nine subjects with chronic obstructive pulmonary disease (COPD) and pulsus paradoxus, M-mode echocardiograms showed inspiratory augmentation of right ventricular dimensions and inspiratory decrease of left ventricular diastolic dimensions. In five subjects in whom the echocardiographic transistor was in the subxiphoid position, mean right ventricular dimensions increased during inspiration from 1.4 +/- 0.20 to 2.96 +/- 0.38 cm (p < 0.01). With inspiration, mean left ventricular diastolic dimensions decreased from 4.8 +/- 0.61 to 3.7 +/- 0.63 cm (p < 0.01) in these five subjects. Two-dimensional echocardiograms, performed in three subjects, confirmed inspiratory augmentation of right ventricular cross-sectional area. Similar changes were produced in two normal volunteers by artificial obstruction to breathing. Left ventricular ejection time measurements demonstrated an inspiratory decline in left ventricular stroke volume. Inspiratory filling of the right ventricle is not hampered, but rather is exaggerated in patients with COPD and pulsus paradoxus, and left ventricular stroke volume is reduced during inspiration. Exaggerated variations in intrathoracic pressure alone did not explain pulsus paradoxus. Increased right ventricular filling and stroke volume during inspiration probably play a part.
Adult rats were exposed to an aerosol of 10% papain for 8 h twice in a 2-wk interval. The control rats were exposed to isotonic saline in the same manner. Three weeks after the final exposure rats were divided into four groups: emphysema-fed, emphysema-starved, control-fed, and control-starved. Starved animals received one-third of their measured daily food consumption and water ad libitum for 6 wk. Final body weight, dry and wet weights of lungs and postfixation lung volume (VL) were significantly lower in starved rats. Dry-to-wet weight ratios were not significantly different among the groups, but VL/body weight was significantly higher in starved animals. Elastic recoil pressure of lung tissue determined in saline-filled lungs decreased and chord compliance over mid- and high-volume ranges increased significantly in starved animals both in control and emphysema groups. Mean linear intercept of air spaces was greater and internal surface area was smaller in starved rats in each group. Therefore, it appears that starvation aggravates the preexisting emphysematous processes in rat lungs.
A B S T R A C T Phagocytosis by rabbit alveolar macrophages (AM) is accompanied by increases in 02 consumption, glucose oxidation, and H202 formation. Two aspects of the interrelations between these metabolic features of phagocytosis have been studied.First, the following evidence indicates that glutathione, glutathione reductase, and peroxidase serve as a cytoplasmic shuttle between H202 and NADPH-dependent glucose oxidation: (a) AM contain 5.9 mi'moles of reduced glutathione per 108 cells and exhibit glutathione peroxidase and NADPH-specific glutathione reductase activity; (b) oxidized glutathione potentiates NADP stimulation of glucose oxidation; (c) an artificial H202-generating system stimulates glucose oxidation; (d) the cell penetrating thiol inhibitor, N-ethylmaleimide diminishes glucose oxidation. This effect largely depends on inhibition of the glutathione system rather than on inhibition of either H202 formation or enzymes directly subserving glucose oxidation.Second, three potential H202-generating oxidases have been sought. No cyanide-insensitive NADH or NADPH oxidase activity could be detected. D-amino acid oxidase activity was 0.48 ±0.07 U/106 cells with D-alanine as substrate.
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