Pulmonary Interstitial Spaces and Lymphatics

Taylor, Aubrey E.; Parker, James C.

doi:10.1002/cphy.cp030104

Cited by 40 publications

(64 citation statements)

References 390 publications

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“…Weight gains during the high PIP ventilation periods were also variable between experiments. Thus the W/D weight ratio is a more variable and less specific indicator of vascular permeability than the K f measurements (62). However, the trends in W/D weight ratios support the concept that PI3K and Src inhibition reduced vascular injury and Akt inhibition augmented injury.…”

Section: Resultsmentioning

confidence: 82%

“…is a sensitive measurement of endothelial hydraulic conductivity in fully recruited lungs because filtration is dependent on the equivalent pore radius to the fourth power (62). After an isogravimetric state is attained, Ppv is increased by 6 cmH 2O for 20 min, and the change in capillary pressure is determined by double occlusion before and after the Ppv increase.…”

Section: Methodsmentioning

confidence: 99%

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Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungs

Miyahara¹,

Hamanaka²,

Weber³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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To determine the role of phosphoinositide 3-OH kinase (PI3K) pathways in the acute vascular permeability increase associated with ventilator-induced lung injury, we ventilated isolated perfused lungs and intact C57BL/6 mice with low and high peak inflation pressures (PIP). In isolated lungs, filtration coefficients ( Kf) increased significantly after ventilation at 30 cmH2O (high PIP) for successive periods of 15, 30 (4.1-fold), and 50 (5.4-fold) min. Pretreatment with 50 μM of the PI3K inhibitor, LY-294002, or 20 μM PP2, a Src kinase inhibitor, significantly attenuated the increase in Kf, whereas 10 μM Akt inhibitor IV significantly augmented the increased Kf. There were no significant differences in Kf or lung wet-to-dry weight (W/D) ratios between groups ventilated with 9 cmH2O PIP (low PIP), with or without inhibitor treatment. Total lung β-catenin was unchanged in any low PIP isolated lung group, but Akt inhibition during high PIP ventilation significantly decreased total β-catenin by 86%. Ventilation of intact mice with 55 cmH2O PIP for up to 60 min also increased lung vascular permeability, indicated by increases in lung lavage albumin concentration and lung W/D ratios. In these lungs, tyrosine phosphorylation of β-catenin and serine/threonine phosphorylation of Akt, glycogen synthase kinase 3β (GSK3β), and ERK1/2 increased significantly with peak effects at 60 min. Thus mechanical stress activation of PI3K and Src may increase lung vascular permeability through tyrosine phosphorylation, but simultaneous activation of the PI3K-Akt-GSK3β pathway tends to limit this permeability response, possibly by preserving cellular β-catenin.

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Section: Resultsmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungs

Miyahara¹,

Hamanaka²,

Weber³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…According to some authors, the pulmonary lymphatic system plays a role of removal of fluids from the abundant peribronchovascular or pleural connective tissue. It is also believed that fluid normally leaks out of capillaries located in the alveolar walls, moves out from very small septal interstitial spaces, and enters lymphatic capillaries in the vicinity of interstitial spaces and thereafter reaches larger lymphatics (Taylor and Parker 1985). The role of the deep distribution of intralobular lymphatics would be to collect the interstitial fluid and proteins very close to or within the interalveolar septa.…”

Section: Discussionmentioning

confidence: 99%

Intralobular Pulmonary Lymphatic Distribution in Normal Human Lung Using D2-40 Antipodoplanin Immunostaining

Kambouchner

Bernaudin

2009

J Histochem Cytochem.

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It has been assumed for a long time that except for limited areas close to respiratory bronchioles or their satellite arteries, there is no evidence of lymphatic vessels deep in the pulmonary lobule. An immunohistochemical study using the D2-40 monoclonal antibody was performed on normal pulmonary samples obtained from surgical specimens, with particular attention to the intralobular distribution of lymphatic vessels. This study demonstrated the presence of lymphatics not only in the connective tissue surrounding the respiratory bronchioles but also associated with intralobular arterioles and/or small veins even less than 50 μm in diameter. A few interlobular lymphatic vessels with a diameter ranging from 10 μm to 20 μm were also observed further away, in interalveolar walls. In conclusion, this study, using the D2-40 monoclonal antibody, demonstrated the presence of small lymphatic channels within the normal human pulmonary lobules, emerging from interalveolar interstitium, and around small blood vessels constituting the paraalveolar lymphatics. This thin intralobular lymphatic network may play a key pathophysiological role in a wide variety of alveolar and interstitial lung diseases and requires further investigation. (J Histochem Cytochem 57:643–648, 2009)

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“…Plasma electrolytes have a value of zero, whereas albumin, the most abundant plasma protein, has an observed value of at least 0.65 in the pulmonary circulation, [see (217) and (65)], depending on species and methodology used for the determination. As protein concentration in pulmonary interstitium is about 0.6 times that of blood plasma (192), the effective oncotic pressure difference σ(π c − π i ) is positive (190,266) and therefore counteracts fluid filtration under physiological conditions. The main determinant of filtration in the intact lung is the transmural hydrostatic pressure difference, (P c -P i ).…”

Section: Lung Fluid Balance the Starling Forcesmentioning

confidence: 99%

“…The main determinant of filtration in the intact lung is the transmural hydrostatic pressure difference, (P c -P i ). The interstitial pressure P i in most systemic vascular beds is negative (10) and in the pulmonary vascular bed, it measures about -10 cmH 2 O under physiological conditions (180,181,266). The negative P i value adds to P c and thus increases the net hydrostatic pressure gradient (i.e., P c − P i ) acting across lung microvasculature.…”

Section: Lung Fluid Balance the Starling Forcesmentioning

confidence: 99%

Cytoskeletal Dynamics and Lung Fluid Balance

Vogel

Malik

2012

Comprehensive Physiology

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This article examines the role of the endothelial cytoskeleton in the lung's ability to restrict fluid and protein to vascular space at normal vascular pressures and thereby to protect lung alveoli from lethal flooding. The barrier properties of microvascular endothelium are dependent on endothelial cell contact with other vessel-wall lining cells and with the underlying extracellular matrix (ECM). Focal adhesion complexes are essential for attachment of endothelium to ECM. In quiescent endothelial cells, the thick cortical actin rim helps determine cell shape and stabilize endothelial adherens junctions and focal adhesions through protein bridges to actin cytoskeleton. Permeability-increasing agonists signal activation of "small GTPases" of the Rho family to reorganize the actin cytoskeleton, leading to endothelial cell shape change, disassembly of cortical actin rim, and redistribution of actin into cytoplasmic stress fibers. In association with calcium- and Src-regulated myosin light chain kinase (MLCK), stress fibers become actinomyosin-mediated contractile units. Permeability-increasing agonists stimulate calcium entry and induce tyrosine phosphorylation of VE-cadherin (vascular endothelial cadherin) and β-catenins to weaken or pull apart endothelial adherens junctions. Some permeability agonists cause latent activation of the small GTPases, Cdc42 and Rac1, which facilitate endothelial barrier recovery and eliminate interendothelial gaps. Under the influence of Cdc42 and Rac1, filopodia and lamellipodia are generated by rearrangements of actin cytoskeleton. These motile evaginations extend endothelial cell borders across interendothelial gaps, and may initiate reannealing of endothelial junctions. Endogenous barrier protective substances, such as sphingosine-1-phosphate, play an important role in maintaining a restrictive endothelial barrier and counteracting the effects of permeability-increasing agonists.

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Pulmonary Interstitial Spaces and Lymphatics

Cited by 40 publications

References 390 publications

Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungs

Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungs

Intralobular Pulmonary Lymphatic Distribution in Normal Human Lung Using D2-40 Antipodoplanin Immunostaining

Cytoskeletal Dynamics and Lung Fluid Balance

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