Effect of colchicine on secretion of alveolar surfactant in intact and regenerating rat lungs

Electron microscopy showed that colchicin in a total dose of 0.6 mg/100 g body weight of noninbred male white rats inhibited alveolar surfactant secretion into the alveolar lumen in both intact and regenerating lungs. This was associated with a partial or complete alveolar collapse. In the course of inhibition of surfactant secretion, on the apical surface of type II alveolocytes there was an activation of surfactant secretion by way of exocytosis into the interstitial space in the basal part of the cells. Disintegration of the collagenous and elastic fibers as well as disturbance of the membranes occurred in the areas where the material of lipid character and products of its metabolism appeared. A hypothesis is suggested about the possible role of such a disturbance in the character and level of alveolar surfactant secretion in the development of lung abnormality under the effect of the factors inactivating the cytoplasmatic micro tubules.     

Malnutrition impairs alveolar fluid clearance in rat lungs

Inadequate nutrition complicates the clinical course of critically ill patients, and many of these patients develop pulmonary edema. However, little is known about the effect of malnutrition on the mechanisms that resolve alveolar edema. Therefore, we studied the mechanisms responsible for the decrease in alveolar fluid clearance in rats exposed to malnutrition. Rats were allowed access to water, but not to food, for 120 h. Then, the left and right lungs were isolated for the measurement of lung water volume and alveolar fluid clearance, respectively. The rate of alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue dye that was instilled into the distal air spaces with an isosmolar 5% albumin solution over 1 h. Malnutrition decreased alveolar fluid clearance by 38% compared with controls. Amiloride (10(-3) M) abolished alveolar fluid clearance in malnourished rats. Either refeeding for 120 h following nutritional deprivation for 120 h or an oral supply of sodium glutamate during nutritional deprivation for 120 h restored alveolar fluid clearance to 91 and 86% of normal, respectively. Dibutyryl-cGMP, a cyclic nucleotide-gated cation channel agonist, increased alveolar fluid clearance in malnourished rats supplied with sodium glutamate. Terbutaline, a beta(2)-adrenergic agonist, increased alveolar fluid clearance in rats under all conditions (control, malnutrition, refeeding, and glutamate-treated). These results indicate that malnutrition impairs primarily amiloride-insensitive and dibutyryl-cGMP-sensitive alveolar fluid clearance, but this effect is partially reversible by refeeding, treatment with sodium glutamate, or beta-adrenergic agonist therapy.     

Mechanisms of alveolar protein clearance in the intact lung

Transport of protein across the alveolar epithelial barrier is a critical process in recovery from pulmonary edema and is also important in maintaining the alveolar milieu in the normal healthy lung. Various mechanisms have been proposed for clearing alveolar protein, including transport by the mucociliary escalator, intra-alveolar degradation, or phagocytosis by macrophages. However, the most likely processes are endocytosis across the alveolar epithelium, known as transcytosis, or paracellular diffusion through the epithelial barrier. This article focuses on protein transport studies that evaluate these two potential mechanisms in whole lung or animal preparations. When protein concentrations in the air spaces are low, e.g., albumin concentrations <0.5 g/100 ml, protein transport demonstrates saturation kinetics, temperature dependence indicating high energy requirements, and sensitivity to pharmacological agents that affect endocytosis. At higher concentrations, the protein clearance rate is proportional to protein concentration without signs of saturation, inversely related to protein size, and insensitive to endocytosis inhibition. Temperature dependence suggests a passive process. Based on these findings, alveolar albumin clearance occurs by receptor-mediated transcytosis at low protein concentrations but proceeds by passive paracellular mechanisms at higher concentrations. Because protein concentrations in pulmonary edema fluid are high, albumin concentrations of 5 g/100 ml or more, clearance of alveolar protein occurs by paracellular pathways in the setting of pulmonary edema. Transcytosis may be important in regulating the alveolar milieu under nonpathological circumstances. Alveolar degradation may become important in long-term protein clearance, clearance of insoluble proteins, or under pathological conditions such as immune reactions or acute lung injury. acute respiratory distress syndrome; endocytosis; diffusion; protein transport pulmonary edema     

Lipids in the lungs and alveolar surfactant in anaphylactic shock

The process of anaphylactoid response of rats to introduction of egg protein is associated with a decrease of the pulmonary surfactant surface activity. The factors of metabolic surfactant inactivation are as follows: protein accumulation, the disturbance of lipids transport between pulmonary cells and alveolar surface, change in fatty-acidic composition of surfactant phospholipids. The isolation of arachidonic acid from surfactant phospholipids in anaphylactoid shock is an evidence for the participation of the pulmonary surface-active phase in the process of biosynthesis of the lipid mediators in respiratory organs.