Transport properties of alveolar epithelium measured by molecular hetastarch absorption in isolated rat lungs

Conhaim, Robert L.; Watson, Kal E.; Lai-Fook, S. J.; Harms, Bruce A.

doi:10.1152/jappl.2001.91.4.1730

Cited by 13 publications

(16 citation statements)

References 16 publications

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“…These other proteins for the most part would be proteins such as immunoglobulins that are larger than albumin. Thus rat, rabbit, dog, pig, and human studies provide evidence that protein clearance from the air spaces of the lung is size dependent (17,27,28,30,37,84).…”

Section: Size Dependencementioning

confidence: 97%

“…Bignon and colleagues (7,8) were the first of several investigators (17,46) to report that alveolar type I and type II cells contained endogenous albumin and immunoglobulins in intracellular vesicles. Micrographs of protein in vesicles demonstrate that the alveolar epithelium is capable of endocytosis of serum protein but do not establish whether the protein is transported across the epithelium, indicate the direction of transport, nor quantify how much protein is transported.…”

Section: Vesicles Vs Channelsmentioning

confidence: 99%

“…We can demonstrate this point with a few simple calculations, using results from a study that modeled large pore frequency in the lung. Conhaim and coworkers (17) made theoretical calculations of the number and size of pores necessary to support the observed transport rates of varioussized hetastarch molecules across the alveolar epithelial barrier in rat lungs (Table 1). On the basis of their modeling work, we estimate that one of these large pores would be found in the alveolar epithelium on average in a volume of 3.5 ϫ 10 Ϫ10 ml (per pore).…”

Section: Vesicles Vs Channelsmentioning

confidence: 99%

“…In a study of pulmonary absorption of different-sized fluorescein isothiocyanate (FITC)-labeled dextrans, Ohtani and colleagues (66) found that rate of absorption decreased with increasing molecular size. Conhaim and colleagues (17) found that transport of differentsized hetastarch molecules out of the alveoli could be modeled by a system of epithelial pores of at least two sizes, 5 and 17 nm in radius, allowing size-dependent variation in the rate of passage. Hastings and colleagues (37) reported an inverse relationship between the Stokes radius and the amount of radiolabeled protein tracer that remained in the lungs of anesthetized rabbits 8 h after instillation.…”

Section: Size Dependencementioning

confidence: 99%

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Mechanisms of alveolar protein clearance in the intact lung

Hastings¹,

Folkesson²,

Matthay³

2004

American Journal of Physiology-Lung Cellular and Molecular Phys

104

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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.

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Section: Size Dependencementioning

confidence: 97%

Section: Vesicles Vs Channelsmentioning

confidence: 99%

Section: Vesicles Vs Channelsmentioning

confidence: 99%

Section: Size Dependencementioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of alveolar protein clearance in the intact lung

Hastings¹,

Folkesson²,

Matthay³

2004

American Journal of Physiology-Lung Cellular and Molecular Phys

104

View full text Add to dashboard Cite

show abstract

“…In a previous report, we characterized the transport properties of this barrier and found that molecules larger than 200 kd were able to cross it (18). In a previous report, we characterized the transport properties of this barrier and found that molecules larger than 200 kd were able to cross it (18).…”

Section: Discussionmentioning

confidence: 81%

Inhaled Thrombolytics Reduce Lung Microclot and Leukocyte Infiltration After Acute Blood Loss

Conhaim

Watson

Dovi

et al. 2014

Shock

Self Cite

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We showed previously that a 30% blood loss in rats, without resuscitation, caused significant accumulation of microthrombi and leukocytes within the pulmonary circulation by 24 h. We hypothesized that the microthrombi formed spontaneously as a consequence of hemorrhage-induced stasis within the low-pressure pulmonary circuit and that the leukocytes were attracted to them. This suggested that elimination of the microthrombi, using an inhaled thrombolytic agent, could prevent the neutrophil sequestration after blood loss. To test this hypothesis, we removed 30% of the calculated blood volume from isoflurane-anesthetized, male Sprague-Dawley rats (350-500 g) over 5 min and allowed them to recover. Six hours later, we re-anesthetized the rats and nebulized tissue plasminogen activator (80 or 320 µg/kg), lactated Ringer's solution (LRS), or ipratropium bromide (i-bromide) into their lungs. We used i-bromide as a control after we discovered that nebulized LRS had thrombolytic properties. At 24 h, we removed and fixed the lungs and prepared sections for immunohistochemistry using antibodies against fibrinogen (microthrombi) and CD16 (leukocytes). Digital images of each section were obtained using a confocal microscope. Pixel counts of the images showed significantly less accumulation of microthrombi and leukocytes in lungs nebulized with tissue plasminogen activator or LRS than in non-nebulized lungs or in lungs nebulized with i-bromide (P ≤ 0.05). Lactated Ringer's solution becomes positively charged when nebulized (unlike i-bromide), suggesting that it eliminated microthrombi by fibrin depolymerization. We confirmed this using an in vitro assay. Our results demonstrate that lyses of microthrombi that accumulate in the lung after acute blood loss prevent subsequent leukocyte sequestration.

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Bacteremia Does Not Affect Cellular Uptake of Ultrafine Particles in the Lungs of Rats

Conhaim

Dovi

Watson

et al. 2010

The Anatomical Record

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To assess the effects of intra-abdominal bacteremia on lung cellular function in vivo, we used electron microscopy to quantify the uptake of 6 nm diameter, albumin-coated colloidal gold particles (overall diam. 20.8 nm) by cells in the lungs of rats made septic by the introduction of live bacteria (E.coli and B. fragilis) into their abdomens. Gold particles were instilled into the trachea 24 hr after bacteremia induction, and lungs were harvested and prepared for electron microscopy 24 hr later. Because bacteremia produces an increase in metabolism, we hypothesized that this might be associated with increased cellular uptake of these particles and also with increased permeability of the alveolar epithelial barrier to them, as bacteremia is also associated with lung injury. We quantified particle uptake by counting particle densities (particles/lm 2 ) within type I and type II epithelial cells, capillary endothelial cells, erythrocytes and neutrophils in the lungs of five septic rats and five sham-sepsis controls. We also counted particle densities within organelles of these cells (nuclei, mitochondria, type II cell lamellar bodies) and within the alveolar interstitium. We found particles to be present within all of these compartments, although we found no differences in particle densities between bacteremic rats and sham-sepsis controls. Our results suggest that these 6 nm particles were able to freely cross cell and organelle membranes, and further suggest that this ability was not altered by bacteremia. Anat Rec, 294:550-557, 2011. V V C 2010 Wiley-Liss, Inc.

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Transport properties of alveolar epithelium measured by molecular hetastarch absorption in isolated rat lungs

Cited by 13 publications

References 16 publications

Mechanisms of alveolar protein clearance in the intact lung

Mechanisms of alveolar protein clearance in the intact lung

Inhaled Thrombolytics Reduce Lung Microclot and Leukocyte Infiltration After Acute Blood Loss

Bacteremia Does Not Affect Cellular Uptake of Ultrafine Particles in the Lungs of Rats

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