Cellular and subcellular localizations of annexins I, IV, and VI in lung epithelia

1996 ◽  
Vol 270 (5) ◽  
pp. L863-L871 ◽  
Author(s):  
N. Mayran ◽  
V. Traverso ◽  
S. Maroux ◽  
D. Massey-Harroche
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Type I ◽  
Type Ii ◽  
Ciliated Cells ◽  
Alveolar Cells ◽  
Annexin I ◽  
Type Ii Pneumocytes ◽  
Immunofluorescence Labeling

The cellular and subcellular localizations of annexins I, IV, and VI in the rabbit tracheal and alveolar epithelia were studied by performing immunofluorescence labeling on thin frozen sections of these tissues, using specific monoclonal antibodies. Annexin I was highly expressed by ciliated cells, where it was concentrated in the cilia but was also present along the basolateral domain of the plasma membrane and in the nuclei. It was also abundant in the cytoplasm of type II pneumocytes and alveolar macrophages. Either one or both of these alveolar cells might be capable of secreting a very small amount of annexin I, which was found to be associated with the surfactant layer. Annexin IV was synthesized by all the lung epithelial cells. It was associated with the plasma membrane basolateral domain in ciliated cells and with either the apical or basal domain of plasma membrane in type I pneumocytes, whereas it was cytoplasmic in goblet cells and type II pneumocytes. Annexin VI was expressed only by alveolar endothelial cells, where it was probably cytoplasmic. None of these three annexins seem to be expressed in the nondifferentiated tracheal basal epithelial cells.

In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cells

2004 ◽  
Vol 286 (5) ◽  
pp. L1045-L1054 ◽  
Author(s):  
Jason M. Roper ◽  
Dawn J. Mazzatti ◽  
Richard H. Watkins ◽  
William M. Maniscalco ◽  
Peter C. Keng ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transmembrane Protein ◽  
Dna Integrity ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Cells ◽  
Endogenous Expression

It is well established that hyperoxia injures and kills alveolar endothelial and type I epithelial cells of the lung. Although type II epithelial cells remain morphologically intact, it remains unclear whether they are also damaged. DNA integrity was investigated in adult mice whose type II cells were identified by their endogenous expression of pro-surfactant protein C or transgenic expression of enhanced green fluorescent protein. In mice exposed to room air, punctate perinuclear 8-oxoguanine staining was detected in ∼4% of all alveolar cells and in 30% of type II cells. After 48 or 72 h of hyperoxia, 8-oxoguanine was detected in 11% of all alveolar cells and in >60% of type II cells. 8-Oxoguanine colocalized by confocal microscopy with the mitochondrial transmembrane protein cytochrome oxidase subunit 1. Type II cells isolated from hyperoxic lungs exhibited nuclear DNA strand breaks by comet assay even though they were viable and morphologically indistinguishable from cells isolated from lungs exposed to room air. These data reveal that type II cells exposed to in vivo hyperoxia have oxidized and fragmented DNA. Because type II cells are essential for lung remodeling, our findings raise the possibility that they are proficient in DNA repair.

scholarly journals TM4SF5-mediated CD44v8-10 splicing variant promotes survival of type II alveolar epithelial cells during idiopathic pulmonary fibrosis

2019 ◽  
Vol 10 (9) ◽  
Author(s):  
Ji Eon Kim ◽  
Hye-Jin Kim ◽  
Jae Woo Jung ◽  
Dae-Geun Song ◽  
Dasomi Park ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Fate ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Type I ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Primary Mouse

Abstract Reactive oxygen species (ROS) regulate cell fate, although signaling molecules that regulate ROS hormesis remain unclear. Here we show that transmembrane 4 L six family member 5 (TM4SF5) in lung epithelial cells induced the alternatively spliced CD44v8-10 variant via an inverse ZEB2/epithelial splicing regulatory proteins (ESRPs) linkage. TM4SF5 formed complexes with the cystine/glutamate antiporter system via TM4SF5- and CD44v8-10-dependent CD98hc plasma-membrane enrichment. Dynamic TM4SF5 binding to CD98hc required CD44v8-10 under ROS-generating inflammatory conditions. TM4SF5 and CD44v8-10 upregulated cystine/glutamate antiporter activity and intracellular glutathione levels, leading to ROS modulation for cell survival. Tm4sf5-null mice exhibited attenuated bleomycin-induced pulmonary fibrosis with lower CD44v8-10 and ESRPs levels than wild-type mice. Primary mouse alveolar epithelial cells (AECs) revealed type II AECs (AECII), but not type I, to adapt the TM4SF5-mediated characteristics, suggesting TM4SF5-mediated AECII survival following AECI injury during idiopathic pulmonary fibrosis (IPF). Thus, the TM4SF5-mediated CD44v8-10 splice variant could be targeted against IPF.

scholarly journals TRIM72 modulates caveolar endocytosis in repair of lung cells

2016 ◽  
Vol 310 (5) ◽  
pp. L452-L464 ◽  
Author(s):  
Nagaraja Nagre ◽  
Shaohua Wang ◽  
Thomas Kellett ◽  
Ragu Kanagasabai ◽  
Jing Deng ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Cell Injury ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Functional Domain ◽  
Physical Interaction ◽  
Type I ◽  
Alveolar Epithelial ◽  
Lung Epithelial

Alveolar epithelial and endothelial cell injury is a major feature of the acute respiratory distress syndrome, in particular when in conjunction with ventilation therapies. Previously we showed [Kim SC, Kellett T, Wang S, Nishi M, Nagre N, Zhou B, Flodby P, Shilo K, Ghadiali SN, Takeshima H, Hubmayr RD, Zhao X. Am J Physiol Lung Cell Mol Physiol 307: L449–L459, 2014.] that tripartite motif protein 72 (TRIM72) is essential for amending alveolar epithelial cell injury. Here, we posit that TRIM72 improves cellular integrity through its interaction with caveolin 1 (Cav1). Our data show that, in primary type I alveolar epithelial cells, lack of TRIM72 led to significant reduction of Cav1 at the plasma membrane, accompanied by marked attenuation of caveolar endocytosis. Meanwhile, lentivirus-mediated overexpression of TRIM72 selectively increases caveolar endocytosis in rat lung epithelial cells, suggesting a functional association between these two. Further coimmunoprecipitation assays show that deletion of either functional domain of TRIM72, i.e., RING, B-box, coiled-coil, or PRY-SPRY, abolishes the physical interaction between TRIM72 and Cav1, suggesting that all theoretical domains of TRIM72 are required to forge a strong interaction between these two molecules. Moreover, in vivo studies showed that injurious ventilation-induced lung cell death was significantly increased in knockout (KO) TRIM72KO and Cav1KO lungs compared with wild-type controls and was particularly pronounced in double KO mutants. Apoptosis was accompanied by accentuation of gross lung injury manifestations in the TRIM72KO and Cav1KO mice. Our data show that TRIM72 directly and indirectly modulates caveolar endocytosis, an essential process involved in repair of lung epithelial cells through removal of plasma membrane wounds. Given TRIM72's role in endomembrane trafficking and cell repair, we consider this molecule an attractive therapeutic target for patients with injured lungs.

scholarly journals Regulation of Lysosome-Associated Membrane Protein 3 (LAMP3) in Lung Epithelial Cells by Coronaviruses (SARS-CoV-1/2) and Type I Interferon Signaling

2021 ◽  
Author(s):  
Chilakamarti V. Ramana
Keyword(s):  
Epithelial Cells ◽  
Viral Entry ◽  
Human Lung ◽  
Type I Interferon ◽  
Respiratory Viruses ◽  
Lung Epithelial Cells ◽  
Type I ◽  
Type Ii ◽  
Interferon Signaling ◽  
Lung Epithelial

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major risk factor for mortality and morbidity in critical care hospitals around the world. Lung epithelial type II cells play a major role in several physiological processes, including recognition and clearance of respiratory viruses as well as repair of lung injury in response to environmental toxicants. Gene expression profiling of lung epithelial type II-specific genes led to the identification of lysosomal-associated membrane protein 3 (LAMP3). Intracellular locations of LAMP3 include plasma membrane, endosomes, and lysosomes. These intracellular organelles are involved in vesicular transport and facilitate viral entry and release of the viral RNA into the host cell cytoplasm. In this study, regulation of LAMP3 expression in human lung epithelial cells by several respiratory viruses and type I interferon signaling was investigated. Coronaviruses including SARS-CoV-1 and SARS-CoV-2 significantly induced LAMP3 expression in lung epithelial cells within 24 hours after infection that required the presence of ACE2 viral entry receptor. Time-course experiments revealed that the induced expression of LAMP3 by SARS-CoV-2 was correlated with the induced expression of interferon-beta1 (IFNB1) and signal transducers and activator of transcription 1 (STAT1) mRNA levels. LAMP3 was also induced by direct IFN-beta treatment or by infection with influenza virus lacking the non-structural protein1(NS1) in NHBE bronchial epithelial cells. LAMP3 expression was induced in human lung epithelial cells by several respiratory viruses, including respiratory syncytial virus (RSV) and the human parainfluenza virus 3 (HPIV3). Location in lysosomes and endosomes as well as induction by respiratory viruses and type I Interferon suggests that LAMP3 may have an important role in inter-organellar regulation of innate immunity and a potential target for therapeutic modulation in health and disease. Furthermore, bioinformatics revealed that a subset of lung type II cell genes were differentially regulated in the lungs of COVID-19 patients.

scholarly journals Expression of ACE2, the SARS-CoV-2 receptor, and TMPRSS2 in prostate epithelial cells

2020 ◽  
Author(s):  
Hanbing Song ◽  
Bobak Seddighzadeh ◽  
Matthew R. Cooperberg ◽  
Franklin W. Huang
Keyword(s):  
Sex Differences ◽  
Epithelial Cells ◽  
Cell Types ◽  
Preliminary Evidence ◽  
Lung Epithelial Cells ◽  
Type Ii ◽  
Double Positive ◽  
Prostate Epithelial Cells ◽  
Type Ii Pneumocytes ◽  
Lung Epithelial

AbstractThe COVID-19 pandemic has spread across more than 200 countries and resulted in over 170,000 deaths. For unclear reasons, higher mortality rates from COVID-19 have been reported in men compared to women. While the SARS-CoV-2 receptor ACE2 and serine protease TMPRSS2 have been detected in lung and other tissues, it is not clear what sex differences may exist. We analyzed a publicly-available normal human prostate single-cell RNA sequencing dataset and found TMPRSS2 and ACE2 co-expressing cells in epithelial cells, with a higher proportion in club and hillock cells. Then we investigated datasets of lung epithelial cells and also found club cells co-expressing TMPRSS2 and ACE2. A comparison of ACE2 expression in lung tissue between males and females showed higher expression in males and a larger proportion of ACE2+ cells in male type II pneumocytes, with preliminary evidence that type II pneumocytes of all lung epithelial cell types showed the highest expression of ACE2. These results raise the possibility that sex differences in ACE2 expression and the presence of double-positive cells in the prostate may contribute to the observed disparities of COVID-19.

Hyperplasia of Type II Pneumocytes in Pulmonary Lymphangioleiomyomatosis

2000 ◽  
Vol 124 (11) ◽  
pp. 1642-1648 ◽  
Author(s):  
Kazuhiro Matsui ◽  
William K. Riemenschneider ◽  
Stephen L. Hilbert ◽  
Zu-Xi Yu ◽  
Kazuyo Takeda ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Connective Tissue ◽  
Structural Characteristics ◽  
Alveolar Epithelial Cells ◽  
Nuclear Antigen ◽  
Type I ◽  
Type Ii ◽  
Electron Microscopic ◽  
Type Ii Pneumocytes ◽  
Microscopic Studies

Abstract Background.—Little is known of the morphology of the pneumocytes lining the parenchymal cysts in lymphangioleiomyomatosis (LAM). Objective.—To evaluate the structural characteristics of the alveolar epithelial cells in LAM. Methods.—Immunohistochemical and electron microscopic studies were performed on lung tissue from 22 women with pulmonary LAM. Results.—Epithelial cells that reacted with PE-10 (a mouse monoclonal antibody that recognizes the surfactant apoprotein A in type II pneumocytes) and TTF-1 (an antibody that identifies nuclear transcription factor found in type II pneumocytes) were the predominant cell type lining the surfaces of lesions of LAM and normal areas of lung. Scanning and transmission electron microscopic studies confirmed that these cells were type II pneumocytes as demonstrated by (1) apical microvilli, (2) electron-dense lamellar bodies, and (3) cytoplasmic projections that extended from the basal surfaces into the underlying connective tissue, where they made extensive contact with interstitial connective tissue cells. A few cells had morphologic characteristics of type I pneumocytes, including large flat surfaces lacking microvilli. Cells that appeared intermediate between type I and type II pneumocytes were observed occasionally. Conclusions.—These observations and the reactivity of these cells with antibody to proliferating cell nuclear antigen demonstrate that extensive hyperplasia of type II pneumocytes is a major characteristic of LAM.

scholarly journals Single-cell analysis of human lung epithelia reveals concomitant expression of the SARS-CoV-2 receptor ACE2 with multiple virus receptors and scavengers in alveolar type II cells

2020 ◽  
Author(s):  
Guangchun Han ◽  
Ansam Sinjab ◽  
Warapen Treekitkarnmongkol ◽  
Patrick Brennan ◽  
Kieko Hara ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Cell ◽  
Expression Patterns ◽  
Severe Pneumonia ◽  
Lung Epithelial Cells ◽  
Chronic Obstructive ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii ◽  
Lung Epithelial

ABSTRACTThe novel coronavirus SARS-CoV-2 was identified as the causative agent of the ongoing pandemic COVID 19. COVID-19-associated deaths are mainly attributed to severe pneumonia and respiratory failure. Recent work demonstrated that SARS-CoV-2 binds to angiotensin converting enzyme 2 (ACE2) in the lung. To better understand ACE2 abundance and expression patterns in the lung we interrogated our in-house single-cell RNA-sequencing dataset containing 70,085 EPCAM+ lung epithelial cells from paired normal and lung adenocarcinoma tissues. Transcriptomic analysis revealed a diverse repertoire of airway lineages that included alveolar type I and II, bronchioalveolar, club/secretory, quiescent and proliferating basal, ciliated and malignant cells as well as rare populations such as ionocytes. While the fraction of lung epithelial cells expressing ACE2 was low (1.7% overall), alveolar type II (AT2, 2.2% ACE2+) cells exhibited highest levels of ACE2 expression among all cell subsets. Further analysis of the AT2 compartment (n = 27,235 cells) revealed a number of genes co-expressed with ACE2 that are important for lung pathobiology including those associated with chronic obstructive pulmonary disease (COPD; HHIP), pneumonia and infection (FGG and C4BPA) as well as malarial/bacterial (CD36) and viral (DMBT1) scavenging which, for the most part, were increased in smoker versus light or non-smoker cells. Notably, DMBT1 was highly expressed in AT2 cells relative to other lung epithelial subsets and its expression positively correlated with ACE2. We describe a population of ACE2-positive AT2 cells that co-express pathogen (including viral) receptors (e.g. DMBT1) with crucial roles in host defense thus comprising plausible phenotypic targets for treatment of COVID-19.

scholarly journals Histo-Morphology Study of the Respiratory Portion of Goat Lung (Capra Hircus) in Baghdad Province

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Noor Yousif
Keyword(s):  
Epithelial Cells ◽  
Squamous Epithelium ◽  
Alveolar Epithelium ◽  
Clara Cell ◽  
Capra Hircus ◽  
Type I ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Pulmonary Parenchyma ◽  
I Cells

The Histo-mrphology were directed on the pneumonic alveoli of 6 male goats. The respiratory portion is composed of typical cuboidal epithelial cells with Clara cell, however, alveolar ducts are lined by simple squamous epithelium and alveoli were generally circular structures that opened into the alveolar conduits and alveolar sacs or respiratory bronchioles. Alveoli were made out of two kinds of cells for example Type-I pneumocytes and Type-II pneumocytes. Previous framed the mainlining epithelial cells of alveoli which were squamous in sort having noticeable perinuclear territory and central found the core, while the last were cuboidal fit as a fiddle with the midway found core and periodically found among the Sort I cells in the alveolar epithelium. The lung pulmonary parenchyma was enveloped by the mesothelium (squamous epithelium) layer of visceral pleura.

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