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.

T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma

Abstract: Background: Asthma is an inflammatory airway disease associated with an infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (ECs). Objective: Shedding of bronchial ECs is characterized by loss of the normal bronchial pseudostratified epithelium and the maintenance of a few basal cells on a thickened basement membrane. The aim of this study was to investigate whether, and by which mechanism, T cells and eosinophils can cause damage to airway ECs. Methods: Bronchial ECs, cultured and exposed to cytokines, eosinophil cationic protein, activated T cells, and eosinophils were studied for the expression of apoptosis receptors (flow cytometry, immunoblotting, and RNA expression) and for the susceptibility for undergoing apoptosis. In addition, bronchial biopsy specimens from patients with asthma were evaluated for EC apoptosis. Results: We demonstrate herein that the respiratory epithelium is an essential target of the inflammatory attack by T cells and eosinophils. Bronchial ECs underwent cytokine-induced cell death with DNA fragmentation and morphologic characteristics of apoptosis mediated by activated T cells and eosinophils. T cell- and eosinophil-induced EC apoptosis was blocked by inhibition of IFN-γ and TNF-α; the Fas ligand-Fas pathway appears to be less important. Recombinant eosinophil cationic protein induced mainly necrosis of ECs. Furthermore, we demonstrated in situ apoptotic features of ECs in bronchial biopsy specimens of asthmatic patients. Conclusion: T cell- and eosinophil-induced apoptosis represents a key pathogenic event leading to EC shedding in asthma. (J Allergy Clin Immunol 2002;109:329-37.)

Differential permeability of endothelial and epithelial barriers to albumin flux

Abstract: We measured the flux of albumin between the vascular space and the pulmonary interstitial and luminal lining fluids in 20 adult sheep with chronic lung lymph fistulas. We sampled the bronchoalveolar lining layer by episodic fiberbronchoscopic lavage. A total of 62 alveolar lavages were performed at times ranging between 30 min and 60 h after intra-arterial injection of 100 microCi of 125I-labeled albumin. Samples of lymph and plasma were obtained simultaneously with lavage fluid, and the radioactivity and albumin content of all samples were measured and expressed as specific activity (counts/min . g albumin). We found that alveolar lavage fluid collected by our technique is not significantly contaminated by plasma or interstitial fluid proteins. Proteins present in alveolar lavage fluid and also present in plasma reach the alveolar space by a normal diffusive process, and not as a result of epithelial membrane damage occurring at the time of lavage. Lung epithelial permeability to albumin in small, but finite (4.3--5.8 x 10(-10) cm/s). Virtually all (greater than 92%) of resistance to albumin flux across the alveolocapillary membrane lies in the epithelial barrier. Increases in permeability of the respiratory epithelium, even minor, would have a marked effect on water and solute balance in the lung. Epithelial injury will potentiate pulmonary edema formation even in the presence of normal pulmonary microvascular pressure, plasma oncotic pressure, and endothelial permeability.

Innate immune responses of airway epithelium to house dust mite are mediated through β-glucan–dependent pathways

Abstract: Background House dust mite (HDM) induces allergic asthma in sensitized individuals, although the mechanisms by which HDM is sensed and recognized by the airway mucosa, leading to dendritic cell (DC) recruitment, activation, and subsequent T H 2-mediated responses, are unknown. Objective We sought to define the pathways by which HDM activates respiratory epithelium to induce allergic airway responses. Methods Using a human airway epithelial cell line (16HBE14o-), we studied secretion of the DC chemokine CCL20 after exposure to HDM or other allergens, investigated components of the HDM responsible for the induction of chemokine release, and examined activation of signaling pathways. Central findings were also confirmed in primary human bronchial cells. Results We demonstrate that exposure of airway epithelium to HDM results in specific and rapid secretion of CCL20, a chemokine attractant for immature DCs. The induction of CCL20 secretion is dose and time dependent and quite specific to HDM because other allergens, such as ragweed pollen and cockroach antigen, fail to significantly induce CCL20 secretion. Induction of CCL20 secretion is not protease or Toll-like receptor 2/4 dependent but, interestingly, relies on β-glucan moieties within the HDM extract, as evidenced by the ability of other β-glucans to competitively inhibit its secretion and by the fact that disruption of these structures by treatment of HDM with β-glucanase significantly reduces subsequent chemokine secretion. Conclusion Taken together, our results describe a novel mechanism for specific pattern recognition of HDM-derived β-glucan moieties, which initiates allergic airway inflammation and, through recruitment of DCs, might link innate pattern recognition at the airway surface with adaptive immune responses.

Modification of gene expression of the small airway epithelium in response to cigarette smoking

Abstract: The earliest morphologic evidence of changes in the airways associated with chronic cigarette smoking is in the small airways. To help understand how smoking modifies small airway structure and function, we developed a strategy using fiberoptic bronchoscopy and brushing to sample the human small airway (10th-12th order) bronchial epithelium to assess gene expression (Affymetrix HG-U133A and HG-133 Plus 2.0 array) in phenotypically normal smokers (n = 16, 25 +/- 7 pack-years) compared to matched nonsmokers (n = 17). Compared to samples from large (second to third order) bronchi, the small airway samples had a higher proportion of ciliated cells, but less basal, undifferentiated, and secretory cells, and contained Clara cells. Even though the smokers were phenotypically normal, microarray analysis of gene expression of the small airway epithelium of the smokers compared to the nonsmokers demonstrated up- and downregulation of genes in multiple categories relevant to the pathogenesis of chronic obstructive lung disease (COPD), including genes coding for cytokines/innate immunity, apoptosis, mucin, response to oxidants and xenobiotics, and general cellular processes. In the context that COPD starts in the small airways, these gene expression changes in the small airway epithelium in phenotypically normal smokers are candidates for the development of therapeutic strategies to prevent the onset of COPD.

Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation

Abstract: In response to infections and irritants, the respiratory epithelium releases the alarmin interleukin (IL)-33 to elicit a rapid immune response. However, little is known about the regulation of IL-33 following its release. Here we report that the biological activity of IL-33 at its receptor ST2 is rapidly terminated in the extracellular environment by the formation of two disulphide bridges, resulting in an extensive conformational change that disrupts the ST2 binding site. Both reduced (active) and disulphide bonded (inactive) forms of IL-33 can be detected in lung lavage samples from mice challenged with Alternaria extract and in sputum from patients with moderate-severe asthma. We propose that this mechanism for the rapid inactivation of secreted IL-33 constitutes a 'molecular clock' that limits the range and duration of ST2-dependent immunological responses to airway stimuli. Other IL-1 family members are also susceptible to cysteine oxidation changes that could regulate their activity and systemic exposure through a similar mechanism.