scholarly journals Frank Low and the first images of the ultrastructure of the pulmonary blood-gas barrier

2016 ◽  
Vol 310 (5) ◽  
pp. L387-L392 ◽  
Author(s):  
John B. West
Keyword(s):  
Extracellular Matrix ◽  
Alveolar Epithelium ◽  
Capillary Endothelium ◽  
Blood Gas ◽  
Major Event ◽  
Gas Barrier ◽  
Pulmonary Physiology ◽  
Pulmonary Capillary ◽  
Matrix Layer ◽  
First Time

Frank N. Low (1911–1998) has the distinction of publishing the first electron micrographs showing the ultrastructure of the pulmonary capillary and particularly the blood-gas barrier. This work in 1952 and 1953 was enabled by the progress in fixation and staining of tissue made by George Palade and was part of the very rapid advance in electron microscopy during the previous 25 years. Low's micrographs clearly showed the three layers of the blood-gas barrier: capillary endothelium, extracellular matrix, and alveolar epithelium. The images immediately resolved the debate about the composition of the blood-gas barrier that had been raging for 100 years. The first published micrographs were rather poor, but the quality rapidly improved and a major event was the first electron micrograph of the human blood-gas barrier published in 1953. These images had an enormous influence on the development of pulmonary physiology and biology. For example, for the first time it became clear that the barrier separating the blood from the alveolar gas was vanishingly thin. The discovery of the extracellular matrix layer ultimately clarified how this barrier, despite its extraordinary thinness, was sufficiently strong to avoid mechanical failure. Despite the major advances made by Low, his name is almost unknown in pulmonary physiology and biology, and perhaps this tribute will help to give him his due.

Thickness of the blood-gas barrier in premature and 1-day-old newborn rabbit lungs

2003 ◽  
Vol 285 (1) ◽  
pp. L130-L136 ◽  
Author(s):  
Zhenxing Fu ◽  
Gregory P. Heldt ◽  
John B. West
Keyword(s):  
Pulmonary Circulation ◽  
Alveolar Epithelium ◽  
Capillary Endothelium ◽  
Blood Gas ◽  
Gas Barrier ◽  
Newborn Rabbit ◽  
Pulmonary Capillaries ◽  
Normal Gestation ◽  
Neonatal Lungs ◽  
Extensive Pilot

The pulmonary capillaries of neonatal lungs are potentially vulnerable to stress failure because of the complex changes in the pulmonary circulation that occur at birth. We studied the ultrastructure of the blood-gas barrier (BGB) in premature and 1-day-old rabbit lungs and compared it with the ultrastructure of adult lungs. Normal gestation of rabbits is 30 days. After extensive pilot measurements, three premature (27 days gestation) and three newborn (1 day old) rabbit lungs were perfusion-fixed at arterial, venous, and airway pressures of 25, 0, and 10 cmH2O, respectively, and the measurements were compared with those of three adult lungs. The thickness of the capillary endothelium, alveolar epithelium, and interstitium of the BGB was measured at right angles to the barrier at random points. A striking finding was the large number of measurements of the interstitial thickness in 1-day-old lungs that were very thin (0–0.1 μm). The percentages of occurrence of very thin interstitium in premature, 1-day-old, and adult lungs were 35.3 ± 9.4, 71.7 ± 5.2, and 43.0 ± 2.6, respectively ( P < 0.02 for 1 day old vs. premature and adult). Given the previously found relationship between stress failure and interstitial thickness, this large proportion of very thin interstitial layers in the capillaries of 1-day-old lungs is a reasonable explanation for their previously demonstrated vulnerability to stress failure.

Solute conductance of blood-gas barrier in hamsters exposed to hyperoxia

1986 ◽  
Vol 60 (6) ◽  
pp. 1908-1916 ◽  
Author(s):  
D. Wangensteen ◽  
R. Piper ◽  
J. A. Johnson ◽  
A. A. Sinha ◽  
D. Niewoehner
Keyword(s):  
Bovine Serum Albumin ◽  
Alveolar Epithelium ◽  
Capillary Endothelium ◽  
Blood Gas ◽  
Lung Weight ◽  
Gas Barrier ◽  
Functional Changes ◽  
Isolated Perfused Lung ◽  
Perfused Lung ◽  
Wet Weight

Hamsters were exposed to greater than 95% O2 continuously for up to 5 days to determine longitudinal changes in the diffusive conductance of the alveolar epithelium and capillary endothelium as a result of hyperoxia. Permeability X surface area (PS, cm3/s X 10(-4)) was measured by isolated, perfused lung techniques. Alveolar epithelium PS for [14C]sucrose and 125I-bovine serum albumin (BSA) were determined at seven exposure times. Control PS (sucrose) and PS(BSA) averaged 1.00 and 0.022, respectively. Values were unchanged until 4.5 days, when significant increases in both, but especially PS(BSA), occurred. After 5 days, PS values were 4.69 and 0.691, respectively. Capillary endothelium PS for 125I-BSA and fluoresceinisothiocyanate dextran-150 (D-150) were measured at four exposure times. Control endothelium PS(BSA) and PS(D-150) averaged 0.232 and 0.048, respectively. These values were also unchanged after 4 days but increased to 0.440 and 0.131 after 5 days. Wet lung weight significantly increased after only 4 days. Hyperoxia thus increased both endothelium and epithelium PS, but epithelium changes were much greater. These functional changes do not occur for several days, occur simultaneously, and follow increases in lung wet weight.

Ultrastructural appearances of pulmonary capillaries at high transmural pressures

1991 ◽  
Vol 71 (2) ◽  
pp. 573-582 ◽  
Author(s):  
K. Tsukimoto ◽  
O. Mathieu-Costello ◽  
R. Prediletto ◽  
A. R. Elliott ◽  
J. B. West
Keyword(s):  
Autologous Blood ◽  
Alveolar Epithelium ◽  
Basement Membranes ◽  
Capillary Endothelium ◽  
Blood Gas ◽  
Gas Barrier ◽  
Pulmonary Capillaries ◽  
The Mean ◽  
Cell Lining

Electronmicroscopic appearances of pulmonary capillaries were studied in rabbit lungs perfused in situ when the capillary transmural pressure (Ptm) was systematically raised from 12.5 to 72.5 +/- 2.5 cmH2O. The animals were anesthetized and exsanguinated, and after the chest was opened, the pulmonary artery and left atrium were cannulated and attached to reservoirs. The lungs were perfused with autologous blood for 1 min, and this was followed by saline-dextran and then buffered glutaraldehyde to fix the lungs for electron microscopy. Normal appearances were seen at 12.5 cmH2O Ptm. At 52.5 and 72.5 cmH2O Ptm, striking discontinuities of the capillary endothelium and alveolar epithelium were seen. A few disruptions were seen at 32.5 cmH2O Ptm (mostly in one animal), but the number of breaks per millimeter cell lining increased markedly up to 72.5 cmH20 Ptm, where the mean frequency was 27.8 +/- 8.6 and 13.6 +/- 1.4 (SE) breaks/mm for endothelium and epithelium, respectively. In some instances, all layers of the blood-gas barrier were disrupted and erythrocytes could be seen moving into the alveolar spaces. In about half the endothelial and epithelial breaks, the basement membranes remained intact. The average break lengths for both endothelium and epithelium did not change significantly with pressure. The width of the blood-gas barrier increased at 52.5 and 72.5 cmH2O Ptm as a result of widening of the interstitium caused by edema. The cause of the disruptions is believed to be stress failure of the capillary wall. The results show that high capillary hydrostatic pressures cause major changes in the ultrastructure of the walls of the capillaries, leading to a high-permeability form of edema.

A morphometric study of the lungs of different sized bats: correlations between structure and function of the chiropteran lung

1991 ◽  
Vol 333 (1266) ◽  
pp. 31-50 ◽  
Keyword(s):  
Surface Area ◽  
Body Mass ◽  
Lung Volume ◽  
Capillary Blood ◽  
The Body ◽  
Capillary Endothelium ◽  
Diffusing Capacity ◽  
Blood Gas ◽  
Pulmonary Capillary ◽  
Pulmonary Capillary Blood

1. The lungs of four species of bats, Phyllostomus hastatus (PH, mean body mass, 98 g), Pteropus lylei (PL,456 g), Pteropus alecto (PA, 667 g), and Pteropus poliocephalus (PP, 928 g) were analysed by morphometric methods. These data increase fivefold the range of body masses for which bat lung data are available, and allow more representative allometric equations to be formulated for bats. 2. Lung volume ranged from 4.9 cm 3 for PH to 39 cm 3 for PP. The volume density of the lung parenchyma (i.e. the volume proportion of the parenchyma in the lung) ranged from 94% in PP to 89% in PH. Of the components of the parenchyma, the alveoli composed 89% and the blood capillaries about 5% . 3. The surface area of the alveoli exceeded that of the blood—gas (tissue) barrier and that of the capillary endothelium whereas the surface area of the red blood cells as well as that of the capillary endothelium was greater than that of the tissue barrier. PH had the thinnest tissue barrier (0.1204 μm) and PP had the thickest (0.3033 μm). 4. The body mass specific volume of the lung, that of the volume of pulmonary capillary blood, the surface area of the blood-gas (tissue) barrier, the diffusing capacity of the tissue barrier, and the total morphometric pulmonary diffusing capacity in PH all substantially exceeded the corresponding values of the pteropid species (i.e. PL, PA and PP). This conforms with the smaller body mass and hence higher unit mass oxygen consumption of PH, a feature reflected in the functionally superior gas exchange performance of its lungs. 5. Morphometrically, the lungs of different species of bats exhibit remarkable differences which cannot always be correlated with body mass, mode of flight and phylogeny. Conclusive explanations of these pulmonary structural disparities in different species of bats must await additional physiological and flight biomechanical studies. 6. While the slope, the scaling factor (b), of the allometric equation fitted to bat lung volume data (b = 0.82) exceeds the value for flight Vo 2max , (b = 0.70), those for the surface area of the blood-gas (tissue) barrier (b = 0.74), the pulmonary capillary blood volume (b = 0.74), and the total morphometric lung diffusing capacity for oxygen (b = 0.69) all correspond closely to the Vo 2max , value. 7 Allometric comparisons of the morphometric pulmonary parameters of bats, birds and non-flying mammals reveal that superiority of the bat lung over that of the non-flying mammal. However, the bat parameters relative to those of non-flying mammals deteriorate towards the higher body size range, because of the generally steeper slopes of the equations for non-flying mammals. Allometric comparisons also reveal that small-size bats have, in general, better adapted lungs than birds of equivalent size but at the higher body mass scale, bats are generally inferior to birds.

Extracellular matrix biology in the lung

1996 ◽  
Vol 270 (1) ◽  
pp. L3-L27 ◽  
Author(s):  
S. E. Dunsmore ◽  
D. E. Rannels
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Current Knowledge ◽  
Biological Effects ◽  
Alveolar Epithelium ◽  
Basement Membranes ◽  
Model Systems ◽  
Capillary Endothelium ◽  
Future Research ◽  
Membrane Components

The lung and other organs are comprised of both cellular and extracellular compartments. Interaction of these components modulates physiological function at the organ, cellular, and subcellular levels. Extracellular components in the gas-exchange region of the lung include both noncellular interstitium and basement membranes. Connective tissue elements of the interstitium in part determine ventilatory function by contributions to tissue compliance and to resistance of the diffusion barrier. The basement membrane underlies cells of both the alveolar epithelium and the capillary endothelium; basement membrane components exert biological effects on adjacent cells through receptor-mediated interactions. This review emphasizes current knowledge concerning the composition and biological activity of extracellular matrix in the alveolar region of the lung. Matrix synthesis and turnover are also considered. Directions for future research are suggested in the context of current knowledge of the lung and other model systems.

Role of the fragility of the pulmonary blood-gas barrier in the evolution of the pulmonary circulation

2013 ◽  
Vol 304 (3) ◽  
pp. R171-R176 ◽  
Author(s):  
John B. West
Keyword(s):  
Pulmonary Circulation ◽  
Complete Separation ◽  
Blood Gas ◽  
Gas Barrier ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Resolution Electron ◽  
Two Factors ◽  
Key Factor ◽  
Capillary Pressures

In 1953 Frank Low published the first high-resolution electron micrographs of the human pulmonary blood-gas barrier. These showed that a structure only 0.3-μm thick separated the capillary blood from the alveolar gas, immediately suggesting that the barrier might be vulnerable to mechanical failure if the capillary pressure increased. However, it was 38 years before stress failure was recognized. Initially it was implicated in the pathogenesis of High Altitude Pulmonary Edema, but it was soon clear that stress failure of pulmonary capillaries is common. The vulnerability of the blood-gas barrier is a key factor in the evolution of the pulmonary circulation. As evolution progressed from the ancestors of fishes to amphibians, reptiles, and finally birds and mammals, two factors challenged the integrity of the barrier. One was the requirement for the barrier to become increasingly thin because of the greater oxygen consumption. The other was the high pulmonary capillary pressures that were inevitable before there was complete separation of the pulmonary and systemic circulations.

scholarly journals Featured Article: Immunomodulatory effect of hemozoin on pneumocyte apoptosis via CARD9 pathway, a possibly retarding pulmonary resolution

2018 ◽  
Vol 243 (5) ◽  
pp. 395-407 ◽  
Author(s):  
Sitang Maknitikul ◽  
Natthanej Luplertlop ◽  
Urai Chaisri ◽  
Yaowapa Maneerat ◽  
Sumate Ampawong
Keyword(s):  
A549 Cells ◽  
Alveolar Epithelium ◽  
Annexin V ◽  
Type Ii ◽  
Blood Gas ◽  
Gas Barrier ◽  
Acridine Orange Staining ◽  
Barrier Breakdown ◽  
E Cadherin

Plasmodium falciparum, the most virulent malaria parasite species, causes severe symptoms especially acute lung injury (ALI), of which characterized by alveolar epithelium and endothelium destruction and accelerated to blood–gas-barrier breakdown. Parasitized erythrocytes, endothelial cells, monocytes, and cytokines are all involved in this mechanism, but hemozoin (HZ), the parasitic waste from heme detoxification, also mainly contributes. In addition, it is not clear why type II pneumocyte proliferation, alveolar restorative stage, is rare in malaria-associated ALI. To address this, in vitro culture of A549 cells with Plasmodium HZ or with interleukin (IL)-1β triggered by HZ and monocytes (HZ-IL-1β) was conducted to determine their alveolar apoptotic effect using ethidium bromide/acridine orange staining, annexin-V-FITC/propidium iodide staining, and electron mircroscopic study. Caspase recruitment domain-containing protein 9 ( CARD9), the apoptotic regulator gene, and IL-1β were quantified by reverse-transcriptase PCR. Junctional cellular defects were characterized by immunohistochemical staining of E-cadherin. The results revealed that cellular apoptosis and CARD9 expression levels were extremely high 24 h after induction by HZ-IL-1β when compared to the HZ- and non-treated groups. E-cadherin was markedly down-regulated by HZ-IL-1β and HZ treatments. CARD9 expression was positively correlated with IL-1β expression and the number of apoptotic cells. Interestingly, the localization of HZ in the vesicular surfactant of apoptotic pneumocyte was also identified and submitted to be a cause of alveolar resolution abnormality. Thus, HZ triggers monocytes to produce IL-1β and induces pneumocyte type II apoptosis through CARD9 pathway in association with down-regulated E-cadherin, which probably impairs alveolar resolution in malaria-associated ALI. Impact statement The present work shows the physical and immunomodulatory properties of hemozoin on the induction of pneumocyte apoptosis in relation to IL-1β production through the CARD9 pathway. This occurrence may be a possible pathway for the retardation of lung resolution leading to blood–gas-barrier breakdown. Our findings lead to the understanding of the host–parasite relationship focusing on the dysfunction in ALI induced by HZ, a possible pathway of the recovering lung epithelial retardation in malaria-associated ARDS.

Ultrastructure of pulmonary microvasculature in acute endotoxemia

1978 ◽  
Vol 36 (2) ◽  
pp. 470-471
Author(s):  
R. G. Gerrity ◽  
M. Richardson
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Alveolar Epithelium ◽  
Endothelial Damage ◽  
Capillary Endothelium ◽  
Type Ii Cells ◽  
Type Ii ◽  
Interstitial Edema ◽  
Pulmonary Capillaries ◽  
Lung Ultrastructure ◽  
Fibrin Thrombi

Dogs were injected intravenously with E_. coli endotoxin (2 mg/kg), and lung samples were taken at 15 min., 1 hr. and 24 hrs. At 15 min., occlusion of pulmonary capillaries by degranulating platelets and polymorphonuclear leukocytes (PML) was evident (Fig. 1). Capillary endothelium was intact but endothelial damage in small arteries and arterioles, accompanied by intraalveolar hemorrhage, was frequent (Fig. 2). Sloughing of the surfactant layer from alveolar epithelium was evident (Fig. 1). At 1 hr., platelet-PML plugs were no longer seen in capillaries, the endothelium of which was often vacuolated (Fig. 3). Interstitial edema and destruction of alveolar epithelium were seen, and type II cells had discharged their granules into the alveoli (Fig. 4). At 24 hr. phagocytic PML's were frequent in peripheral alveoli, while centrally, alveoli and vessels were packed with fibrin thrombi and PML's (Fig. 5). In similar dogs rendered thrombocytopenic with anti-platelet serum, lung ultrastructure was similar to that of controls, although PML's were more frequently seen in capillaries in the former (Fig. 6).

scholarly journals Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maria Hurskainen ◽  
Ivana Mižíková ◽  
David P. Cook ◽  
Noora Andersson ◽  
Chanèle Cyr-Depauw ◽  
...  
Keyword(s):  
Single Cell ◽  
Lung Development ◽  
Alveolar Epithelium ◽  
Cell Types ◽  
Capillary Endothelium ◽  
Stromal Fibroblasts ◽  
Main Driver ◽  
Macrophage Populations ◽  
Induced Changes ◽  
Cellular Compartments

AbstractDuring late lung development, alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired late lung development manifests as bronchopulmonary dysplasia (BPD) in preterm infants. Single-cell RNA sequencing (scRNA-seq) allows for assessment of complex cellular dynamics during biological processes, such as development. Here, we use MULTI-seq to generate scRNA-seq profiles of over 66,000 cells from 36 mice during normal or impaired lung development secondary to hyperoxia with validation of some of the findings in lungs from BPD patients. We observe dynamic populations of cells, including several rare cell types and putative progenitors. Hyperoxia exposure, which mimics the BPD phenotype, alters the composition of all cellular compartments, particularly alveolar epithelium, stromal fibroblasts, capillary endothelium and macrophage populations. Pathway analysis and predicted dynamic cellular crosstalk suggest inflammatory signaling as the main driver of hyperoxia-induced changes. Our data provides a single-cell view of cellular changes associated with late lung development in health and disease.

scholarly journals Mechanical ventilation-induced alterations of intracellular surfactant pool and blood–gas barrier in healthy and pre-injured lungs

2020 ◽  
Author(s):  
Jeanne-Marie Krischer ◽  
Karolin Albert ◽  
Alexander Pfaffenroth ◽  
Elena Lopez-Rodriguez ◽  
Clemens Ruppert ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Blood Gas ◽  
Control Groups ◽  
Gas Barrier ◽  
Alveolar Epithelial ◽  
Alveolar Surfactant ◽  
Healthy Control ◽  
Mean Size ◽  
The Mean ◽  
Injury Progression

AbstractMechanical ventilation triggers the manifestation of lung injury and pre-injured lungs are more susceptible. Ventilation-induced abnormalities of alveolar surfactant are involved in injury progression. The effects of mechanical ventilation on the surfactant system might be different in healthy compared to pre-injured lungs. In the present study, we investigated the effects of different positive end-expiratory pressure (PEEP) ventilations on the structure of the blood–gas barrier, the ultrastructure of alveolar epithelial type II (AE2) cells and the intracellular surfactant pool (= lamellar bodies, LB). Rats were randomized into bleomycin-pre-injured or healthy control groups. One day later, rats were either not ventilated, or ventilated with PEEP = 1 or 5 cmH2O and a tidal volume of 10 ml/kg bodyweight for 3 h. Left lungs were subjected to design-based stereology, right lungs to measurements of surfactant proteins (SP−) B and C expression. In pre-injured lungs without ventilation, the expression of SP-C was reduced by bleomycin; while, there were fewer and larger LB compared to healthy lungs. PEEP = 1 cmH2O ventilation of bleomycin-injured lungs was linked with the thickest blood–gas barrier due to increased septal interstitial volumes. In healthy lungs, increasing PEEP levels reduced mean AE2 cell size and volume of LB per AE2 cell; while in pre-injured lungs, volumes of AE2 cells and LB per cell remained stable across PEEPs. Instead, in pre-injured lungs, increasing PEEP levels increased the number and decreased the mean size of LB. In conclusion, mechanical ventilation-induced alterations in LB ultrastructure differ between healthy and pre-injured lungs. PEEP = 1 cmH2O but not PEEP = 5 cmH2O ventilation aggravated septal interstitial abnormalities after bleomycin challenge.

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