Topic
Respiratory epithelium
About: Respiratory epithelium is a research topic. Over the lifetime, 5048 publications have been published within this topic receiving 222304 citations. The topic is also known as: respiratory tract epithelium & Respiratory Mucosa.
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TL;DR: The respiratory epithelium is a potential site for somatic gene therapy for the common hereditary disorders alpha 1-antitrypsin (alpha 1AT) deficiency and cystic fibrosis by infecting epithelial cells of the cotton rat respiratory tract in vitro and in vivo.
Abstract: The respiratory epithelium is a potential site for somatic gene therapy for the common hereditary disorders alpha 1-antitrypsin (alpha 1AT) deficiency and cystic fibrosis. A replication-deficient adenoviral vector (Ad-alpha 1AT) containing an adenovirus major late promoter and a recombinant human alpha 1AT gene was used to infect epithelial cells of the cotton rat respiratory tract in vitro and in vivo. Freshly isolated tracheobronchial epithelial cells infected with Ad-alpha 1AT contained human alpha 1AT messenger RNA transcripts and synthesized and secreted human alpha 1AT. After in vivo intratracheal administration of Ad-alpha 1AT to these rats, human alpha 1AT messenger RNA was observed in the respiratory epithelium, human alpha 1AT was synthesized and secreted by lung tissue, and human alpha 1AT was detected in the epithelial lining fluid for at least 1 week.
975 citations
TL;DR: The successful establishment of a postcrisis SV40 large T-antigen transformed epithelial cell line derived from human bronchial epithelium is described, and this cell line, 16HBE14o- cells, provides a valuable resource for studying the modulation of CFTR and its role in regulation of chloride ion transport in human airway epithelia as well as other aspects of human airways cell biology.
Abstract: A major limitation in the study of vectorial ion transport, secretion, and differentiated function in the human airway epithelium has been the lack of suitable cell culture systems. Progress in this direction has been made through the transformation of primary cultured epithelial cells. However, these transformants tend to lose differentiated properties with increasing serial passage, particularly following crisis. The suc cessful establishment of a postcrisis SV40 large T-antigen transformed epithelial cell line derived from human bronchial epithelium is described. This cell line, 16HBEI40-, retains differentiated epithelial mor phology and functions. Cell cultures show the presence of tight junctions and cilia, and monolayers gener ate transepithelial resistance, as measured in Ussing chambers, and retain iJ-adrenergic stimulation of cAMP-dependent chloride ion transport, measured either by ,6CI- efflux or as short-circuit current in Ussing chambers. The cells also increase chloride transport in response to bradykinin or calcium iono phore. In addition, 16HBE140-cells express levels of both the cystic fibrosis transmembrane conductance regulator (CFTR) mRNA and protein readily detectable by Northern and Western hybridization analysis, respectively. These cells provide a valuable resource for studying the modulation of CFTR and its role in regulation of chloride ion transport in human airway epithelium as well as other aspects of human airway cell biology. The human airway epithelium is pseudostratified, consisting of highly organized layers of polar cells with specific dif ferentiated functions. It includes ciliated columnar cells, basal cells, and secretory goblet cells that are linked by tight junctions. The tight junctions provide a barrier between the airway lumen and the underlying tissues and divide the epi thelial cells into apical and basolateral domains. Both of these plasma membrane compartments contain different populations of proteins that allow for directional flux of ions
919 citations
TL;DR: It is feasible to use an adenovirus vector to transfer and express the CFTR cDNA in the respiratory epithelium of individuals with CF and Correction of the CF phenotype of the airway epithelia might be achieved with this strategy.
Abstract: We have administered a recombinant adenovirus vector (AdCFTR) containing the normal human CFTR cDNA to the nasal and bronchial epithelium of four individuals with cystic fibrosis (CF). We show that this vector can express the CFTR cDNA in the CF respiratory epithelium in vivo. With doses up to 2 x 10(9) pfu, there was no recombination/complementation or shedding of the vector or rise of neutralizing antibody titres. At 2 x 10(9) pfu, a transient systemic and pulmonary syndrome was observed, possibly mediated by interleukin-6. Follow-up at 6-12 months demonstrated no long term adverse effects. Thus, it is feasible to use an adenovirus vector to transfer and express the CFTR cDNA in the respiratory epithelium of individuals with CF. Correction of the CF phenotype of the airway epithelium might be achieved with this strategy.
839 citations
TL;DR: The data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19, which likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure.
Abstract: To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19
815 citations
TL;DR: Uniform labeling of epithelium in large, cartilaginous airways was found with anti-i-NOS in both human bronchi and normal rat trachea samples, suggesting a constitutive role for a NOS that shares epitope(s) with or is highly homologous to the inducible, macrophage type of NOS.
Abstract: Nitric oxide synthase (NOS) produces nitric oxide, a mediator of potential importance in numerous physiologic and inflammatory processes in the lung. We localized constitutive NOS (c-NOS) and inducible NOS (i-NOS) within lung tissue by immunoperoxidase labeling with specific antibodies or by histochemical demonstration of the characteristic NADPH diaphorase activity of NOS. We analyzed human airway (n = 4) or parenchyma (n = 10) specimens obtained from uninvolved areas of surgical tumor resections. We also studied human fetal lung samples (n = 6) and normal or inflamed (16 h after intratracheal LPS instillation) rat lung tissue. Immunostaining with anti-c-NOS identified c-NOS antigen in rat lung nerves, endothelium, and airway epithelium. Normal or inflamed rat macrophages were not stained. Human nerve elements and large-vessel endothelium showed immunostaining with the anti-c-NOS, but no labeling of the airway or alveolar epithelium was seen. Immunostaining with anti-i-NOS showed strong labeling of rat m...
807 citations