Mechanisms Of Alveolar Protein Clearance In The Intact Lung
acute respiratory distress syndrome; air-blood barrier; apoprotein sp-a; bronchoalveolar lavage fluid; diffusion; endocytosis; epithelial-cell monolayers; ii cells; instillation; intratracheal; junctions; opens tight; perfused rabbit lungs; Physiology; protein; rat lung; Respiratory System; respiratory-distress syndrome; transport pulmonary edema
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.
Hastings R H; Folkesson H G; Matthay M A
American Journal of Physiology-Lung Cellular and Molecular Physiology
2004
2004-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1152/ajplung.00205.2003" target="_blank" rel="noreferrer noopener">10.1152/ajplung.00205.2003</a>
Rapid alveolar epithelial fluid clearance following lung lavage in pulmonary alveolar proteinosis
injury; liquid clearance; Respiratory System; transport; General & Internal Medicine; catecholamines; anesthetized sheep; channels; edema; mechanisms; resolution; rat lung; alveolar epithelial fluid transport; lung lavage; phospholipoproteinosis pulmonary edema; pulmonary alveolar
Study objective: To measure the in vivo rate of alveolar epithelial fluid clearance of the human lung in patients with pulmonary alveolar phospholipoproteinosis (PAP). Design: Prospective clinical study. Setting: The medical-surgical ICUs of a university teaching hospital. Patients: Four patients with idiopathic PAP requiring therapeutic lung lavage. Interventions: Large-volume lung lavage with isotonic saline solution using fiberoptic bronchoscopy followed by serial sampling of alveolar fluid using a wedged bronchial catheter. Measurements and results: The rate of alveolar epithelial fluid clearance was calculated by measuring the concentration of protein in sequential samples. Alveolar epithelial fluid clearance over the first hour after lung lavage was 53 +/- 14% (mean +/- SD). Sequential samples in two patients indicated a sustained high rate of clearance over several hours. Plasma and alveolar fluid epinephrine levels were in the normal range in two patients. Conclusions and significance: Alveolar fluid clearance is rapid after lung lavage in patients with PAP and appears to be driven by catecholamine-independent mechanisms. The rapid rate of alveolar epithelial fluid transport explains why patients with PAP tolerate large-volume lung lavage.
Chesnutt M S; Nuckton T J; Golden J; Folkesson H G; Matthay M A
Chest
2001
2001-07
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1378/chest.120.1.271" target="_blank" rel="noreferrer noopener">10.1378/chest.120.1.271</a>
Lung edema clearance: 20 years of progress selected contribution: Long-term effects of beta(2)-adrenergic receptor stimulation on alveolar fluid clearance in mice
acute lung injury; alveolar; beta-adrenergic-receptor; desensitization; down-regulation; epithelium; hydrostatic pulmonary-edema; in-vivo; liquid clearance; lung fluid balance; messenger-rna; Physiology; pulmonary edema; rat lung; resolution; sodium transport; Sport Sciences
Stimulation of active fluid transport with beta-adrenergic receptor (betaAR) agonists can accelerate the resolution of alveolar edema. However, chronic betaAR-agonist administration may cause betaAR desensitization and downregulation that may impair physiological responsiveness to betaAR-agonist stimulation. Therefore, we measured baseline and terbutaline- (10(-3) M) stimulated alveolar fluid clearance in mice that received subcutaneously (miniosmotic pumps) either saline or albuterol (2 mg.kg(-1).day(-1)) for 1, 3, or 6 days. Continuous albuterol administration increased plasma albuterol levels (10(-5) M), an effect that was associated with 1) a significant decrease in betaAR density and 2) attenuation, but not ablation, of maximal terbutaline- induced cAMP production. Forskolin-mediated cAMP-release was unaffected. Continuous albuterol infusion stimulated alveolar fluid clearance on day 1 but did not increase alveolar fluid clearance on days 3 and 6. However, terbutaline- stimulated alveolar fluid clearance in albuterol-treated mice was not reduced compared with saline-treated mice. Despite significant reductions in betaAR density and agonist-mediated cAMP production by long-term betaAR-agonist exposure, maximal betaAR-agonist-mediated increase in alveolar fluid clearance is not diminished in mice.
Sartori C; Fang X; McGraw D W; Koch P; Snider M E; Folkesson H G; Matthay M A
Journal of Applied Physiology
2002
2002-11
Journal Article
<a href="http://doi.org/10.1152/japplphysiol.00275.2002" target="_blank" rel="noreferrer noopener">10.1152/japplphysiol.00275.2002</a>