New Insight into the Development of the Respiratory Acini in Rabbits: Morphological, Electron Microscopic Studies, and TUNEL Assay

2019 ◽  
Vol 25 (3) ◽  
pp. 769-785 ◽  
Author(s):  
Doaa M. Mokhtar ◽  
Manal T. Hussein ◽  
Marwa M. Hussein ◽  
Enas A. Abd-Elhafez ◽  
Gamal Kamel
Keyword(s):  
Tunel Assay ◽  
Second Phase ◽  
Type I ◽  
Apoptotic Cells ◽  
Clara Cells ◽  
Ciliated Cells ◽  
Blood Capillaries ◽  
Pulmonary Alveoli ◽  
Alveolar Septa ◽  
Terminal Bronchiole

AbstractThis study investigated the histomorphological features of developing rabbit respiratory acini during the postnatal period. On the 1st day of postnatal life, the epithelium of terminal bronchiole consisted of clear cells which intercalated between few ciliated and abundant non-ciliated (Clara) cells. At this age, the rabbit lung was in the alveolar stage. The terminal bronchioles branched into several alveolar ducts, which opened into atria that communicated to alveolar sacs. All primary and secondary inter-alveolar septa were thick and showed a double-capillary network (immature septa). The primitive alveoli were lined largely by type-I pneumocytes and mature type-II pneumocytes. The type-I pneumocytes displayed an intimate contact with the endothelial cells of the blood capillaries forming the blood–air barrier (0.90 ± 0.03 µm in thickness). On the 3rd day, we observed intense septation and massive formation of new secondary septa giving the alveolar sac a crenate appearance. The mean thickness of the air–blood barrier decreased to reach 0.78 ± 0.14 µm. On the 7th day, the terminal bronchiole epithelium consisted of ciliated and non-ciliated cells. The non-ciliated cells could be identified as Clara cells and serous cells. New secondary septa were formed, meanwhile the inter-alveolar septa become much thinner and the air–blood barrier thickness was 0.66 ± 0.03 µm. On the 14th day, the terminal bronchiole expanded markedly and the pulmonary alveoli were thin-walled. Inter-alveolar septa become much thinner and single capillary layers were observed. In the 1st month, the secondary septa increased in length forming mature cup-shaped alveoli. In the 2nd month, the lung tissue grew massively to involve the terminal respiratory unit. In the 3rd month, the pulmonary parenchyma appeared morphologically mature. All inter-alveolar septa showed a single-capillary layer, and primordia of new septa were also observed. The thickness of the air–blood barrier was much thinner; 0.56 ± 0.16 µm. TUNEL assay after birth revealed that the apoptotic cells were abundant and distributed in the epithelium lining of the pulmonary alveoli and the interstitium of the thick interalveolar septa. On the 7th day, and onward, the incidence of apoptotic cells decreased markedly. This study concluded that the lung development included two phases: the first phase (from birth to the 14th days) corresponds to the period of bulk alveolarization and microvascular maturation. The second phase (from the 14th days to the full maturity) corresponds to the lung growth and late alveolarization.

scholarly journals THE ABSORPTION OF PROTEIN SOLUTIONS FROM THE PULMONARY ALVEOLI

1937 ◽  
Vol 66 (4) ◽  
pp. 449-458 ◽  
Author(s):  
Cecil K. Drinker ◽  
Madeleine Field Warren ◽  
Margaret MacLanahan
Keyword(s):  
Thoracic Duct ◽  
Horse Serum ◽  
Molecular Size ◽  
The Other ◽  
Immunological Methods ◽  
Protein Solutions ◽  
Blood Capillaries ◽  
Egg Albumin ◽  
Pulmonary Alveoli ◽  
The Right

Horse serum, crystallized hemoglobin, and crystallized egg albumin have been injected into the lung alveoli of dogs in which the entrances of the right lymphatics have been tied and the thoracic duct cannulated. Samples of blood and lymph have been taken following this injection. Only after several hours in the case of the horse serum and hemoglobin have these proteins been detected by immunological methods and invariably they have appeared first in the blood. Egg albumin also enters the blood capillaries, but much more rapidly than the other two proteins, due probably to the smaller molecular size.

Abstract 276: SR-BI Suppresses Apoptosis by Reducing Endoplasmic Reticulum Stress and Promoting Akt Activity in Macrophages

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Huan Tao ◽  
Patricia G Yancey ◽  
Sean S Davies ◽  
L Jackson Roberts ◽  
John L Blakemore ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Apolipoprotein E ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Free Cholesterol ◽  
Oxidized Ldl ◽  
Tunel Staining ◽  
Type I ◽  
Apoptotic Cells ◽  
Atherosclerotic Lesions

Objective: Macrophage apoptosis contributes to atherosclerotic plaque necrosis, inflammation, development and rupture. Scavenger receptor class B type I (SR-BI) is a key regulator of HDL metabolism and cellular cholesterol homeostasis. Here we examined the hypothesis that macrophage SR-BI modulates lipid-associated cellular stress and apoptosis. Methods and Results: In vitro cell apoptosis assays were performed in primary macrophages, and for in vivo evidence, we examined TUNEL staining of atherosclerotic lesions of LDLR -/- mice that were reconstituted with SR-BI -/- or WT bone marrow after 16 weeks on a Western diet. We found that SR-BI deficiency led to ~64.3% more apoptotic cells induced by oxidized LDL or free cholesterol in primary macrophages, and 6-fold more lesional apoptotic cells in SR-BI -/- →LDLR -/- mice compared to WT recipient mice. In macrophages, SR-BI deficiency caused significant accumulations of cellular free cholesterol and elevated markers of endoplasmic reticulum (ER) stress. These were exacerbated by feeding mice a high-cholesterol diet or inactivating the apolipoprotein E gene. Peroxidation of lipoproteins and cell membranes leads to modification of phosphatidylethanolamine by lipid aldehydes including isolevuglandins (IsoLG-PE). Treatment of macrophages with IsoLG-PE induced 52.6% more apoptotic cells in SR-BI -/- macrophages compared to WT. Transgenic expression of SR-BI by transfection of SR-BI -/- macrophages rescued oxidative stress-induced ER stress and cell apoptosis. SR-BI deficiency inhibited the Akt pathway compromising macrophage survival and increasing lesion necrosis. Moreover, Akt Activator was able to rescue SR-BI deficiency associated apoptosis in macrophages. Apolipoprotein E interacts with SR-BI in macrophages, co-operating for cellular lipid homeostasis and cell survival signaling. Conclusion: SR-BI protects against cell apoptosis induced by lipid stress in macrophages and atherosclerotic lesions. The underlying mechanisms are, at least in part, through reducing lipid-associated ER stress and promoting Akt activity in macrophages. Thus, we identify macrophage SR-BI-mediated apoptosis pathways as molecular targets for the prevention of atherosclerotic cardiovascular events.

scholarly journals Targeting Selectins Mediated Biological Activities With Multivalent Probes

2021 ◽  
Vol 9 ◽  
Author(s):  
Deepak Ganesh ◽  
Prashant Jain ◽  
Chethan Devanur Shanthamurthy ◽  
Suraj Toraskar ◽  
Raghavendra Kikkeri
Keyword(s):  
Tumor Metastasis ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Type I ◽  
Blood Capillaries ◽  
Activated Platelets ◽  
Selectin Ligands ◽  
Different Types ◽  
Selectin Binding ◽  
Sialyl Lewisa

Selectins are type-I transmembrane glycoproteins that are ubiquitously expressed on activated platelets, endothelial cells, and leukocytes. They bind to cell surface glycoproteins and extracellular matrix ligands, regulate the rolling of leukocytes in the blood capillaries, and recruit them to inflammatory sites. Hence, they are potential markers for the early detection and inhibition of inflammatory diseases, thrombosis, cardiovascular disorders, and tumor metastasis. Fucosylated and sialylated glycans, such as sialyl Lewisx, its isoform sialyl Lewisa, and heparan sulfate, are primary selectin ligands. Functionalization of these selectin-binding ligands on multivalent probes, such as nanoparticles, liposomes, and polymers, not only inhibits selectin-mediated biological activity but is also involved in direct imaging of the inflammation site. This review briefly summarizes the selectin-mediated various diseases such as thrombosis, cancer and recent progress in the different types of multivalent probes used to target selectins.

scholarly journals Development and Remodeling of the Vertebrate Blood-Gas Barrier

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Andrew Makanya ◽  
Aikaterini Anagnostopoulou ◽  
Valentin Djonov
Keyword(s):  
Extracellular Proteins ◽  
Appreciable Amount ◽  
Interstitial Tissue ◽  
Type I ◽  
Blood Gas ◽  
Gas Barrier ◽  
Molecular Control ◽  
Blood Capillaries ◽  
Mammalian Lung ◽  
Avian Lung

During vertebrate development, the lung inaugurates as an endodermal bud from the primitive foregut. Dichotomous subdivision of the bud results in arborizing airways that form the prospective gas exchanging chambers, where a thin blood-gas barrier (BGB) is established. In the mammalian lung, this proceeds through conversion of type II cells to type I cells, thinning, and elongation of the cells as well as extrusion of the lamellar bodies. Subsequent diminution of interstitial tissue and apposition of capillaries to the alveolar epithelium establish a thin BGB. In the noncompliant avian lung, attenuation proceeds through cell-cutting processes that result in remarkable thinning of the epithelial layer. A host of morphoregulatory molecules, including transcription factors such as Nkx2.1, GATA, HNF-3, and WNT5a; signaling molecules including FGF, BMP-4, Shh, and TFG-βand extracellular proteins and their receptors have been implicated. During normal physiological function, the BGB may be remodeled in response to alterations in transmural pressures in both blood capillaries and airspaces. Such changes are mitigated through rapid expression of the relevant genes for extracellular matrix proteins and growth factors. While an appreciable amount of information regarding molecular control has been documented in the mammalian lung, very little is available on the avian lung.

Early expression of β- and γ-subunits of epithelial sodium channel during human airway development

2000 ◽  
Vol 278 (1) ◽  
pp. L177-L184 ◽  
Author(s):  
Dominique Gaillard ◽  
Jocelyne Hinnrasky ◽  
Sylvie Coscoy ◽  
Paul Hofman ◽  
Michael A. Matthay ◽  
...  
Keyword(s):  
Human Lung ◽  
Immunohistochemical Localization ◽  
Fluid Composition ◽  
Clara Cells ◽  
Ciliated Cells ◽  
Membrane Protein Complex ◽  
Large Airways ◽  
Early Expression ◽  
Polyclonal Antisera ◽  
Human Airways

The amiloride-sensitive epithelial Na+channel (ENaC) is an apical membrane protein complex involved in active Na+ absorption and in control of fluid composition in airways. There are no data reporting the distribution of its pore-forming α-, β-, and γ-subunits in the developing human lung. With use of two different rabbit polyclonal antisera raised against β- and γ-ENaC, immunohistochemical localization of the channel was performed in fetal (10–35 wk) and in adult human airways. Both subunits were detected after 17 wk of gestation on the apical domain of bronchial ciliated cells, in glandular ducts, and in bronchiolar ciliated and Clara cells. After 30 wk, the distribution of β- and γ-subunits was similar in fetal and adult airways. In large airways, the two subunits were detected in ciliated cells, in cells lining glandular ducts, and in the serous gland cells. In the distal bronchioles, β- and γ-subunits were identified in ciliated and Clara cells. Ultrastructural immunogold labeling confirmed the identification of β- and γ-ENaC proteins in submucosal serous cells and bronchiolar Clara cells. Early expression of ENaC proteins in human fetal airways suggests that Na+ absorption might begin significantly before birth, even if secretion is still dominant.

scholarly journals Nrf2 Overexpression for the Protective Effect of Skin-Derived Precursors against UV-Induced Damage: Evidence from a Three-Dimensional Skin Model

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Dehai Xian ◽  
Xia Xiong ◽  
Jixiang Xu ◽  
Li Xian ◽  
Qirong Lei ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Cell Swelling ◽  
Histological Structure ◽  
Related Factor ◽  
Type I ◽  
Apoptotic Cells ◽  
Ros Scavenging ◽  
Skin Model ◽  
Protective Genes ◽  
3D Skin

Background. Skin photodamage is associated with ultraviolet- (UV-) induced reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (Nrf2) inactivation. In our previous study, skin-derived precursors (SKPs) were shown to ameliorate a UV-induced damage in mice, probably through Nrf2 activation and ROS scavenging. Objective. To clarify the mechanism underlying the photoprotective effect of SKPs against UV-induced damage in a three-dimensional (3D) skin model. Methods. The Nrf2 gene in SKPs was modified using lentiviral infection, and 3D skin models were reconstructed with keratinocytes and fibroblasts on the basis of type I collagen. Subsequently, these models were divided into the following six groups: normal, model, overexpressed, control, silenced, and negative control groups. Prior to irradiation, respective SKPs were injected into the last four groups. Next, all groups except the normal group were exposed to UVA+UVB. Lastly, the pathological and molecular-biological techniques were employed to determine the parameters. Additionally, LY294002, a PI3K inhibitor, was used to investigate the roles of PI3K/Akt and Nrf2/hemeoxygenase-1 (HO-1) in SKP photoprotection. Results. Normal 3D skin models appeared as milky-white analogs with a clear, well-arranged histological structure. After the skin was exposed to irradiation, it exhibited cell swelling and a disorganized structure and developed nuclear condensation with numerous apoptotic cells. The expressions of cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins remarkably decreased, which were accompanied by increased oxidative stress and decreased antioxidants (P<0.05). However, these phenomena were reversed by nrf2-overexpressing SKPs. The 3D skin in the overexpressed group showed mild swelling, neatly arranged cells, and few apoptotic cells. Cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins were highly expressed, and the oxidative biomarkers were remarkably ameliorated (P<0.05). Nevertheless, the expression of these proteins decreased after LY294002 pretreatment regardless of SKP treatment or not. Meanwhile, there were increases in both UV-induced apoptotic cells and ROS level accompanied with SOD and GPX decrease in the presence of LY294002. Conclusions. Evidence from the 3D skin model demonstrates that the protection of SKPs against UV-mediated damage is primarily via the PI3K/Akt-mediated activation of the Nrf2/HO-1 pathway, indicating that SKPs may be a promising candidate for the treatment of photodermatoses.

Postnatal undernutrition slows development of bronchiolar epithelium in rats

1988 ◽  
Vol 255 (4) ◽  
pp. R521-R526 ◽  
Author(s):  
G. D. Massaro ◽  
L. McCoy ◽  
D. Massaro
Keyword(s):  
Small Airway ◽  
Numerical Density ◽  
Clara Cells ◽  
Ciliated Cells ◽  
Long Term Effects ◽  
Chronic Lung Diseases ◽  
Airway Function ◽  
Childhood Environment ◽  
Bronchiolar Epithelium ◽  
Morphological Maturation

The lung's small conducting airways are sites of dysfunction early in the course of chronic lung diseases that are prevalent in humans; furthermore, there is evidence that aspects of childhood environment may adversely influence small airway function in adulthood. Because there is considerable early postnatal morphological maturation of the bronchiolar epithelium in rats, these considerations led to the present study in which we assessed the effect of early postnatal undernutrition in rats on the anatomic development of the bronchiolar epithelium. We found undernutrition, produced by increasing rat litter size shortly after birth, led to delayed development of the mitochondria and rough endoplasmic reticulum of bronchiolar Clara cells. Of particular interest, underfeeding resulted in considerably diminished mitosis by Clara cells, decreased nuclear numerical density of bronchiolar ciliated cells, evidence of diminished conversion of Clara cells to ciliated cells, and an abnormal cellular composition of the small airway epithelium that persisted well beyond the period of underfeeding. We conclude that early neonatal events can have long-term effects on the bronchiolar epithelium.

Rat lungs show a biphasic formation of new alveoli during postnatal development

2014 ◽  
Vol 117 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Stefan A. Tschanz ◽  
Lilian A. Salm ◽  
Matthias Roth-Kleiner ◽  
Sebastien F. Barré ◽  
Peter H. Burri ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Morphological Description ◽  
Published Data ◽  
Second Phase ◽  
Weighted Mean ◽  
Biphasic Pattern ◽  
Rat Lungs ◽  
Alveolar Septa ◽  
Exchange Surface ◽  
Microvascular Maturation

Roughly 90% of the gas-exchange surface is formed by alveolarization of the lungs. To the best of our knowledge, the formation of new alveoli has been followed in rats only by means of morphological description or interpretation of semiquantitative data until now. Therefore, we estimated the number of alveoli in rat lungs between postnatal days 4 and 60 by unambiguously counting the alveolar openings. We observed a bulk formation of new alveoli between days 4 and 21 (17.4 times increase from 0.8 to 14.3 millions) and a second phase of continued alveolarization between days 21 and 60 (1.3 times increase to 19.3 million). The (number weighted) mean volume of the alveoli decreases during the phase of bulk alveolarization from ∼593,000 μm3 at day 4 to ∼141,000 μm3 at day 21, but increases again to ∼298,000 μm3 at day 60. We conclude that the “bulk alveolarization” correlates with the mechanism of classical alveolarization (alveolarization before the microvascular maturation is completed) and that the “continued alveolarization” follows three proposed mechanisms of late alveolarization (alveolarization after microvascular maturation). The biphasic pattern is more evident for the increase in alveolar number than for the formation of new alveolar septa (estimated as the length of the free septal edge). Furthermore, a striking negative correlation between the estimated alveolar size and published data on retention of nanoparticles was detected.

Trichloroethylene induces pulmonary fibrosis in mice

1994 ◽  
Vol 72 (3) ◽  
pp. 205-210 ◽  
Author(s):  
P. G. Forkert ◽  
L. Forkert
Keyword(s):  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Interstitial Fibrosis ◽  
Proline Content ◽  
Collagen Deposition ◽  
Clara Cells ◽  
Elastic Recoil ◽  
Acute Dose ◽  
Lung Structure ◽  
Alveolar Septa

Trichloroethylene elicits acute pulmonary cytotoxicity in mice, which involves Clara cells of bronchioles. In this study, we have examined the effects of an acute dose of trichloroethylene in lungs of mice over 3 months. Pulmonary fibrosis was first detected at 15 days and was progressive with time elapsed after trichloroethylene exposure. Diffuse interstitial fibrosis was observed in the alveolar zone, resulting in thickening of alveolar septa and distortion of lung structure. The fibrosis was most pronounced at 90 days after treatment, resulting in deposition of connective tissue in the alveolar septa. Levels of total lung hydroxyproline were not significantly different in control and treated mice at 30 and 60 days after trichloroethylene treatment, but were significantly increased at 90 days. Proline content remained unchanged during the course of this study. The increase in collagen deposition at 90 days coincided with a signficant increase in lung elastic recoil. Our results show that a single acute dose of trichloroethylene causes structural and functional abnormalities that are progressive for at least 3 months.Key words: trichloroethylene, lung, interstitial fibrosis.

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