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.

NF-κB activation and sustained IL-8 gene expression in primary cultures of cystic fibrosis airway epithelial cells stimulated with Pseudomonas aeruginosa

Abstract: The progression of lung disease in cystic fibrosis (CF) is characterized by an exuberant inflammatory response mounted by the respiratory epithelium that is further exacerbated by bacterial infecti...

Trefoil Factor Family-Peptides Promote Migration of Human Bronchial

Abstract: A process termed “restitution” enables rapid repair of the respiratory epithelium by migration of neighbouring cells. Mucin-associated TFF-peptides (formerly P-domain peptides or trefoil factors) are typical motogens enhancing migration of cells in various in vitro models mimicking restitution of the intestine. The human bronchial epithelial cell line BEAS-2B was used as a model system of airway restitution. The motogenic activities of recombinant human TFF2 as well as porcine TFF2 were demonstrated by in vitro wound healing assays of BEAS-2B cells. TFF2 did not induce phosphorylation of the epidermal growth factor (EGF) receptor. EGF was capable of enhancing the motogenic effect of human TFF2 at a concentration of 3 � 10 � 10 M whereas EGF itself (i.e., in the absence of TFF2) did not stimulate migration at this low concentration. Furthermore, TFF2 as well as monomeric and dimeric forms of TFF3 enhanced migration of BEAS-2B cells in Boyden chambers. Motogenic activity of TFF2 was also shown for normal human bronchial epithelial (NHBE) cells in Boyden chambers. These results suggest that TFF-peptides act as motogens in the human respiratory epithelium triggering rapid repair of damaged mucosa in the course of airway diseases such as asthma. The respiratory epithelium is frequently injured by inhaled toxic agents, by micro-organisms, or during inflammatory diseases such as asthma. This often leads to desquamation of cells from the epithelium and denudation of the basement membrane. Migration of neighboring cells is an important component for the rapid repair of damaged airway epithelium. Rapid re-epithelialization is promoted by microcirculation-derived factors together with an intact basement membrane; this repair starts within minutes after damage, long before cell proliferation can be turned on (1, 2). This process was termed “restitution” (3). Various model systems of restitution in the airway epithelium include primary cultures of human (4), bovine (5), or guinea-pig (6) bronchial epithelial cells; cultured alveolar epithelial cells (7); and in vivo epithelial shedding of guinea-pig trachea (1). Migration is induced by several peptides (“moto

Acute safety and effects on mucociliary clearance of aerosolized uridine 5′-triphosphate ± amiloride in normal human adults

Abstract: Impaired mucociliary clearance contributes to the pathophysiology of several airways diseases including cystic fibrosis, asthma, and chronic bronchitis. Extracellular triphosphate nucleotides (adenosine 5'-triphosphate [ATP], uridine 5'-triphosphate [UTP]) activate several components of the mucociliary escalator, suggesting they may have potential as therapeutic agents for airways diseases. We conducted initial (Phase I) studies of acute safety and efficacy of aerosolized UTP alone and in combination with aerosolized amiloride, the sodium channel blocker, in normal human volunteers. Safety was assessed by measurement of pulmonary function. Neither UTP alone nor in combination with amiloride caused any clinically significant adverse effects on airway mechanics, (subdivisions of) lung volumes, or gas exchange. Acute efficacy of UTP and amiloride alone and in combination, was assessed by measuring changes in the clearance of inhaled radiolabeled particles. A 2.5-fold increase in mucociliary clearance was seen in response to UTP alone and in combination with amiloride. We conclude that aerosolized UTP +/- amiloride clearly enhances mucociliary clearance without acute adverse effects in normal adults, and may have therapeutic potential to enhance airways clearance in diseases characterized by retained airways secretions.

Defective regional immunity in the respiratory tract of neonates is attributable to hyporesponsiveness of local dendritic cells to activation signals.

Abstract: A variety of studies suggest that the increased susceptibility of neonates to allergic and infectious respiratory diseases is due to delayed postnatal maturation of local mucosal immune function. We have recently demonstrated that the postnatal development of the major resident APC population in the respiratory tract (RT), class II MHC (Ia)-bearing dendritic cells (DC), is delayed relative to that in other tissues, and that both the intensity of Ia expression on these RTDC and their density within respiratory epithelia remain low until after weaning. The present study focuses on the functional capacity of neonatal RTDC and their responses to exogenous stimuli, and demonstrates that 1) infant Ia+ RTDC respond poorly to GM-CSF, under conditions that stimulate high levels of Ia expression and concomitant APC activity in adult cells; 2) both infant and adult RTDC contain a subpopulation of Ia- cells recognized by mAb OX62 that also respond poorly to GM-CSF; 3) inhalation of microbial stimuli or parenteral administration of IFN-gamma triggers rapid recruitment of DC into the airway epithelium and lung parenchyma of adults; this response is markedly attenuated in newborns and does not attain levels of competence until after weaning; and 4) endogenous macrophage-mediated suppression of the RTDC response to GM-CSF, the principal mechanism limiting in situ DC functional maturation in the adult lung, is highly active in the neonates. Taken together with earlier evidence of the relatively rapid postnatal development of T and B cell function in these animals, the present findings suggest that the sluggish performance of respiratory mucosal immune function(s) during infancy is attributable primarily to delayed maturation of local DC populations.

A novel ACE2 isoform is expressed in human respiratory epithelia and is upregulated in response to interferons and RNA respiratory virus infection.

Abstract: Angiotensin-converting enzyme 2 (ACE2) is the main entry point in airway epithelial cells for SARS-CoV-2. ACE2 binding to the SARS-CoV-2 protein spike triggers viral fusion with the cell plasma membrane, resulting in viral RNA genome delivery into the host. Despite ACE2's critical role in SARS-CoV-2 infection, full understanding of ACE2 expression, including in response to viral infection, remains unclear. ACE2 was thought to encode five transcripts and one protein of 805 amino acids. In the present study, we identify a novel short isoform of ACE2 expressed in the airway epithelium, the main site of SARS-CoV-2 infection. Short ACE2 is substantially upregulated in response to interferon stimulation and rhinovirus infection, but not SARS-CoV-2 infection. This short isoform lacks SARS-CoV-2 spike high-affinity binding sites and, altogether, our data are consistent with a model where short ACE2 is unlikely to directly contribute to host susceptibility to SARS-CoV-2 infection.