Visualization and quantitative analysis of the alveolar capillary network – Implications for lung developmental biology

Author(s):  
Christian Mühlfeld ◽  
Roman Grothausmann ◽  
Matthias Ochs
2018 ◽  
Author(s):  
Lucia Durrieu ◽  
Daniel Kirrmaier ◽  
Tatjana Schneidt ◽  
Ilia Kats ◽  
Sarada Raghavan ◽  
...  

AbstractEmbryogenesis relies on instructions provided by spatially organized signaling molecules known as morphogens. Understanding the principles behind morphogen distribution and how cells interpret locally this information remains a major challenge in developmental biology. Here we introduce morphogen-age measurements as a novel approach to retrieve key parameters in morphogen dynamics. Using a tandem fluorescent timer (tFT) as a protein-age sensor we find a gradient of increasing age of Bicoid (Bcd) along the anterior-posterior (AP) axis in the early Drosophila embryo. Quantitative analysis retrieves parameter that are most consistent with the synthesis-diffusion-degradation (SDD) model underlying Bcd-gradient formation, and rule out some other hypotheses for gradient formation. Moreover, we show that the timer can detect transitions in the dynamics associated with syncytial cellularization. Our results provide new insight into Bcd gradient formation, and demonstrate how morphogen age-information can complement knowledge about movement, abundance and distribution, which should be widely applicable for other systems.


Author(s):  
A. Shirai ◽  
T. Hayase

It is said that neutrophils, a kind of leukocytes, can be retained in pulmonary alveolar capillary bed, even in normal lungs, resulting in higher concentration than in systemic circulation due to their relatively low deformability, and the concentrated neutrophils help the lung to effectively eliminate the enemies invading from outer air. The authors have developed a model to simulate the flow of neutrophils through an alveolar capillary network, considering the cells’ low deformability as the dominant factor for the retention. Flow of a suspension of neutrophils in plasma through a simplified lattice alveolar capillary network model was numerically simulated to investigate the effect of the retention on the increase in the concentration ratio of the cells between in the network and in the suspension. The numerical result showed that the ratio was lower than the experimentally obtained value. Other possible factors to influence the cell’s retention time are friction and adhesion of the cell on the endothelium. In the last study, effect of the retention time of the cells in individual capillary segments on the increase in the concentration ratio was investigated to suggest the ratio may have an upper limit no matter how long the retention time is extended. In this paper, the authors investigated the contribution of various parameters which affect transit time of a neutrophil through a single capillary segment to the relationships between the retention time and the concentration ratio. Finally, it was shown that the number of cells in the network increased to approach a finite value as the increase in the coefficient, independent of the cell property, concentration of the cells in the suspension or the capillary shape. Transition of the relationship was changed with the parameters.


2015 ◽  
Vol 36 (11) ◽  
pp. 2954-2962 ◽  
Author(s):  
Gitte Nykjær Nikolajsen ◽  
Kamila Anna Kotynski ◽  
Morten Skovgaard Jensen ◽  
Mark J. West

2005 ◽  
Vol 233 (4) ◽  
pp. 1261-1271 ◽  
Author(s):  
Matthias Roth-Kleiner ◽  
Thomas M. Berger ◽  
Mojmir R. Tarek ◽  
Peter H. Burri ◽  
Johannes C. Schittny

2017 ◽  
Vol 312 (2) ◽  
pp. L243-L257 ◽  
Author(s):  
Roman Grothausmann ◽  
Lars Knudsen ◽  
Matthias Ochs ◽  
Christian Mühlfeld

Grothausmann R, Knudsen L, Ochs M, Mühlfeld C. Digital 3D reconstructions using histological serial sections of lung tissue including the alveolar capillary network. Am J Physiol Lung Cell Mol Physiol 312: L243–L257, 2017. First published December 2, 2016; doi: 10.1152/ajplung.00326.2016 .—The alveolar capillary network (ACN) provides an enormously large surface area that is necessary for pulmonary gas exchange. Changes of the ACN during normal or pathological development or in pulmonary diseases are of great functional impact and warrant further analysis. Due to the complexity of the three-dimensional (3D) architecture of the ACN, 2D approaches are limited in providing a comprehensive impression of the characteristics of the normal ACN or the nature of its alterations. Stereological methods offer a quantitative way to assess the ACN in 3D in terms of capillary volume, surface area, or number but lack a 3D visualization to interpret the data. Hence, the necessity to visualize the ACN in 3D and to correlate this with data from the same set of data arises. Such an approach requires a large sample volume combined with a high resolution. Here, we present a technically simple and cost-efficient approach to create 3D representations of lung tissue ranging from bronchioles over alveolar ducts and alveoli up to the ACN from more than 1 mm sample extent to a resolution of less than 1 μm. The method is based on automated image acquisition of serially sectioned epoxy resin-embedded lung tissue fixed by vascular perfusion and subsequent automated digital reconstruction and analysis of the 3D data. This efficient method may help to better understand mechanisms of vascular development and pathology of the lung.


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