Transalveolar transport of large polar solutes (sucrose, inulin, and dextran)

Theodore, Joseph M.; Ed, Robin; Gaudio, Rosa Maria; Acevedo, J.

doi:10.1152/ajplegacy.1975.229.4.989

Cited by 65 publications

(31 citation statements)

References 3 publications

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“…The ratio of epithelial to total ACM resistance to Al PI transport is 0.96-0.98, depending on the method ofcalculation. This ratio is similar to that suggested by Theodore et al (37) for inulin (0.95) and to that calculated by Gorin and Stewart (31) for albumin (0.92). These calculations, as well as the measured levels of antigenic A1PI in sheep lung lymph, demonstrate that the steady-state levels of Al PI in the interstitium following inhalation of Al PI aerosols will be closer to levels of Al PI in plasma than to levels in the alveolus.…”

Section: Resultssupporting

confidence: 92%

Pulmonary deposition and clearance of aerosolized alpha-1-proteinase inhibitor administered to dogs and to sheep.

Smith

Traber²,

Traber³

et al. 1989

J. Clin. Invest.

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Augmentation of lung antiprotease levels may be an important therapeutic intervention in the prevention of pulmonary emphysema. We have administered aerosols of plasma-derived human alpha, proteinase inhibitor (AlPI) to the lungs of dogs and sheep to investigate (a) delivery of the protein to the distal air spaces of the lung, (b) maintenance of functional activity of the protein; and (c) flux of the protein across the components of the alveolar-capillary membrane. AlPI (26.4 mg/kg body weight) was administered as an aerosol to anesthetized animals; sheep were prepared for the chronic collection of lung lymph. Immunoperoxidase staining of lung tissue obtained 2 h after administration of AlPI demonstrated the presence of human AlPI on the surface of alveoli and distal bronchioles. Bronchoalveolar lavage fluid recovered at intervals after AlPI administration demonstrated time-dependent elevations of human AlPI levels with augmentation of lavage fluid antielastase activity in proportion to the content of human AlPI. Using radiolabeled AlPI as a tracer, we found that 32% of the aerosol was retained in the animals' lungs. Measurements of the rate of loss of AlPI from the lung and of the rate of appearance of human AlPI in plasma resulted in a calculated permeability of the alveolar-capillary membrane to AlPI of 3.494-39 X 10-10 cm/s. Experiments using instrumented sheep allowed independent calculation of endothelial permeability to AlPI of 122-236 X 10-10 cm/s and calculation of epithelial permeability of 4.704.81 X 10-10 cm/s. Modeling of aerosol delivery of Al PI to humans using the results of these studies predicts that the ratio of plasma/alveolar levels of delivered AlPI will be 0.024, and that aerosolization of 175 mg AlPI/d will result in an AlPI alveolar fluid level of 1.0 mg/ml. Aerosol administration of AlPI may provide an efficient method of augmenting alveolar antiprotease levels.

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Section: Resultssupporting

confidence: 92%

Pulmonary deposition and clearance of aerosolized alpha-1-proteinase inhibitor administered to dogs and to sheep.

Smith

Traber²,

Traber³

et al. 1989

J. Clin. Invest.

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“…In this regard, Effros and Mason (35), upon analysis of various published data on lung epithelial protein permeability, showed an apparent inverse (albeit not strictly reciprocal) relationship between molecular weight and rate of lung clearance of molecules of different sizes. A later study on alveolar epithelial permeabilities of urea, sucrose, inulin, and dextran (60-90-kDa range) in saline-filled dog lungs also showed a similar relation between the size of molecules and permeabilities (113). In support of these findings, a larger permeability-surface area product for sucrose than for albumin in rabbit lungs was reported (120), and the bioavailability of intratracheally instilled proteins exhibited lower values for larger proteins (42,43).…”

Section: Protein Clearance Studies Using Intact Lung Models Under Nonmentioning

confidence: 72%

Protein transport across the lung epithelial barrier

Kim

Malik

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

181

130

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. Because concentrations of plasma proteins in alveolar fluid can increase in injured lungs (such as with permeability edema and inflammation), understanding how alveolar epithelium handles protein transport is needed to develop therapeutic measures to restore alveolar homeostasis. This review provides an update on recent findings on protein transport across the alveolar epithelial barrier. The use of primary cultured rat alveolar epithelial cell monolayers (that exhibit phenotypic and morphological traits of in vivo alveolar epithelial type I cells) has shown that albumin and IgG are absorbed via saturable processes at rates greater than those predicted by passive diffusional mechanisms. In contrast, secretory component, the extracellular portion of the polymeric immunoglobulin receptor, is secreted into alveolar fluid. Transcytosis involving caveolae and clathrincoated pits is likely the main route of alveolar epithelial protein transport, although relative contributions of these internalization steps to overall protein handling of alveolar epithelium remain to be determined. The specific pathways and regulatory mechanisms responsible for translocation of proteins across lung alveolar epithelium and regulation of the cognate receptors (e.g., 60-kDa albumin binding protein and IgG binding FcRn) expressed in alveolar epithelium need to be elucidated. alveolar epithelial cells; albumin; secretory component; immunoglobulin G MACROMOLECULE TRANSPORT ACROSS alveolar epithelium has been investigated over the years, but little is known to date concerning the mechanisms and underlying pathways regulating transalveolar protein clearance. Alveolar protein clearance is fundamental to the resolution of the transudate and exudate after hydrostatic-and especially high permeability-type pulmonary edema. The inability to clear excess proteins from air spaces is associated with poor prognosis in patients with alveolar flooding pulmonary edema. Clearance of edema fluid via active ion transport processes raises the oncotic pressure that, in the absence of efficient clearance mechanisms for proteins, slows alveolar fluid clearance. Patients with acute respiratory distress syndrome (ARDS), for example, have large quantities of precipitated protein in their air spaces (3), and nonsurvivors have three times more protein in their air spaces than survivors (21). In addition, excess serum proteins in alveolar edema fluid may lead to precipitation and modification of proteins (e.g., by reactive oxygen and nitrogen species). Although macrophages may contribute to clearance of the excess proteins, the integrity of the alveolar epithelial barrier may not be readily re-

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“…In normal individuals, the level of fibronectin/albumin in lavage was an average of 25±3% of that of plasma. Although lung permeability studies with fibronectin have not been carried out, plasma fibronectin has a mol wt of 440,000, and it is known that macromolecules of that size can diffuse from blood into lung, although not as readily as albumin (35,36). Second, fibronectin is a major secretory product of lung fibroblasts (1,5,6), a cell population that represents 35-40% of the parenchymal cells of the normal lung (37).…”

Section: Resultsmentioning

confidence: 99%

“…First, fibronectin is a major secretory product of fibroblasts (1,5,6), a cell population that is expanded in the parenchyma of the lungs of these patients (17). Second, at least some of the interstitial lung diseases are associated with the presence of proteolytic enzymes in the lower respiratory tract (43), thus providing a means by which tissue fibronectin or its fragments could be released to the epithelial surface (35,44,45). Consistent with this concept, some of the antigenic fibronectin found in the lavage fluid of patients with interstitial lung disease is nonfunctional (i.e., binding to collagen is reduced) (Fig.…”

Section: Resultsmentioning

confidence: 99%