Feeling the squeeze: does airway constriction stimulate the bronchial epithelium?

Introduction. Some studies have found that cilia were shorter in COPD smokers than in nonsmokers or healthy smokers. However, the structural abnormalities of cilia and the cause of such abnormalities in COPD patients still remain unknown. Tumor necrosis factor alpha receptor 3 interacting protein 1 (MIP-T3) may play an important role in the progress of ciliary protein transporting. Objectives. This study aimed at exploring the dominated structural abnormalities of cilia and the involvement of MIP-T3 in the pathogenesis of cilia of COPD patients. Methods. Patients who accepted pulmonary lobectomy were divided into 3 groups: the chronic obstructive pulmonary disease (COPD) smoker group, the healthy smoker group, and the nonsmoker group, according to smoking history and pulmonary function. The ultrastructure of cilia and the percentage of abnormal cilia were analyzed using a transmission electron microscope. Real-time PCR, immunohistochemical staining, and western blotting in bronchial epithelium were used to determine MIP-T3 mRNA and protein expression. The relationship between the percentage of abnormal cilia and lung function and MIP-T3 protein expression was analyzed. Results. Patients in the COPD smoker group had increased percentage of abnormal cilia comparing to both the healthy smoker group and the nonsmoker group (both P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P value <0.05). Moreover, the percentage of abnormal cilia was negatively correlated with FEV1, FEV1/FVC ratio, and FEV1%pred (all P values <0.05). Moreover, the MIP-T3 protein expression was positively correlated with the percentage of abnormal cilia (P value <0.05). Conclusions. Our results suggested that the abnormal ciliary ultrastructure, which was common in COPD patients, might be due to MIP-T3 downregulation.

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Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia

Innate Immunity ◽

10.1177/1753425921994906 ◽

2021 ◽

Vol 27 (3) ◽

pp. 251-259

Author(s):

Michael Glöckner ◽

Sebastian Marwitz ◽

Kristina Rohmann ◽

Henrik Watz ◽

Dörte Nitschkowski ◽

...

Keyword(s):

Epithelial Cells ◽

Haemophilus Influenzae ◽

Bronchial Epithelium ◽

Bronchial Epithelial Cells ◽

Respiratory Pathogen ◽

Chronic Obstructive ◽

Bronchial Epithelial ◽

Extracellular Matrix Components ◽

The Impact ◽

Primary Bronchial Epithelial Cells

Non-typeable Haemophilus influenzae (NTHi) is the most common respiratory pathogen in patients with chronic obstructive disease. Limited data is available investigating the impact of NTHi infections on cellular re-differentiation processes in the bronchial mucosa. The aim of this study was to assess the effects of stimulation with NTHi on the bronchial epithelium regarding cellular re-differentiation processes using primary bronchial epithelial cells harvested from infection-free patients undergoing bronchoscopy. The cells were then cultivated using an air-liquid interface and stimulated with NTHi and TGF-β. Markers of epithelial and mesenchymal cells were analyzed using immunofluorescence, Western blot and qRT-PCR. Stimulation with both NTHi and TGF-ß led to a marked increase in the expression of the mesenchymal marker vimentin, while E-cadherin as an epithelial marker maintained a stable expression throughout the experiments. Furthermore, expression of collagen 4 and the matrix-metallopeptidases 2 and 9 were increased after stimulation, while the expression of tissue inhibitors of metallopeptidases was not affected by pathogen stimulation. In this study we show a direct pathogen-induced trans-differentiation of primary bronchial epithelial cells resulting in a co-localization of epithelial and mesenchymal markers and an up-regulation of extracellular matrix components.

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Characterization of adenylyl cyclase isoforms in rat peripheral pulmonary arteries

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.6.l1359 ◽

2001 ◽

Vol 280 (6) ◽

pp. L1359-L1369 ◽

Cited By ~ 32

Author(s):

Karen B. Jourdan ◽

Nicola A. Mason ◽

Lu Long ◽

Peter G. Philips ◽

Martin R. Wilkins ◽

...

Keyword(s):

Smooth Muscle ◽

Adenylyl Cyclase ◽

Pulmonary Arteries ◽

Bronchial Epithelium ◽

Rt Pcr ◽

Bronchial Smooth Muscle ◽

Functional Studies ◽

Kinase C ◽

Rat Lungs

Activation of adenylyl cyclase (AC), of which there are 10 diversely regulated isoforms, is important in regulating pulmonary vascular tone and remodeling. Immunohistochemistry in rat lungs demonstrated that AC2, AC3, and AC5/6 predominated in vascular and bronchial smooth muscle. Isoforms 1, 4, 7, and 8 localized to the bronchial epithelium. Exposure of animals to hypoxia did not change the pattern of isoform expression. RT-PCR confirmed mRNA expression of AC2, AC3, AC5, and AC6 and demonstrated AC7 and AC8 transcripts in smooth muscle. Western blotting confirmed the presence of AC2, AC3, and AC5/6 proteins. Functional studies provided evidence of cAMP regulation by Ca2+ and protein kinase C-activated but not Gi-inhibited pathways, supporting a role for AC2 and a Ca2+-stimulated isoform, AC8. However, NKH-477, an AC5-selective activator, was more potent than forskolin in elevating cAMP and inhibiting serum-stimulated [3H]thymidine incorporation, supporting the presence of AC5. These studies demonstrate differential expression of AC isoforms in rat lungs and provide evidence that AC2, AC5, and AC8 are functionally important in cAMP regulation and growth pathways in pulmonary artery myocytes.

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Stimulation of both human bronchial epithelium and neutrophils is needed for maximal interactive adhesion

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.270.1.l80 ◽

1996 ◽

Vol 270 (1) ◽

pp. L80-L87 ◽

Cited By ~ 5

Author(s):

P. G. Bloemen ◽

M. C. Van den Tweel ◽

P. A. Henricks ◽

F. Engels ◽

M. J. Van de Velde ◽

...

Keyword(s):

Epithelial Cells ◽

Cultured Cells ◽

Bronchial Epithelium ◽

Bronchial Epithelial Cells ◽

Intercellular Adhesion Molecule ◽

Tnf Alpha ◽

Epithelial Cell Line ◽

Ifn Gamma ◽

Bronchial Epithelial ◽

Stimulation Of

It has become clear that the bronchial epithelium is not just a passive barrier but plays an active role in inflammation. It can produce several inflammatory mediators and does express cell adhesion molecules of which intercellular adhesion molecule (ICAM)-1 can be upregulated by cytokines like interferon (IFN)-gamma. In the present study, we analyzed in detail the interaction of neutrophils with human bronchial epithelial cells, both primary cultured cells and the bronchial epithelial cell line BEAS-2B. Confluent monolayers of epithelial cells were incubated with freshly isolated 51Cr-labeled neutrophils for 30 min at 37 degrees C; then the nonadherent cells were removed by washing gently. Stimulation of the epithelial cells with IFN-gamma or the combination of IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) (which doubles the ICAM-1 expression) increased neutrophil adhesion. Activation of the neutrophils themselves with N-formylmethionyl-leucyl-phenylalanine (fMLP), platelet-activating factor, or TNF-alpha also caused a profound enhancement of the adhesion. A significant additional increase was found when the epithelial cells had been exposed to IFN-gamma and the neutrophils were stimulated with fMLP simultaneously. This effect was even more pronounced with epithelium preincubated with IFN-gamma and TNF-alpha. With the use of monoclonal antibodies against CD18 and ICAM-1, it was demonstrated that the increased adhesion was mainly mediated by the ICAM-1/beta 2-integrin interaction. This study highlights that both the activation state of the bronchial epithelial cells and the activation state of the neutrophils are critical for their interactive adhesion.

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Pattern and mechanism of airway response to hypocapnia in normal subjects

Journal of Applied Physiology ◽

10.1152/jappl.1979.47.1.8 ◽

1979 ◽

Vol 47 (1) ◽

pp. 8-12 ◽

Cited By ~ 35

Author(s):

C. F. O'Cain ◽

M. J. Hensley ◽

E. R. McFadden ◽

R. H. Ingram

Keyword(s):

Vital Capacity ◽

Normal Subjects ◽

Oxygen Mixture ◽

Flow Volume ◽

Mixture Density ◽

Lung Capacity ◽

Airway Constriction ◽

Maximal Expiratory Flow ◽

Airway Response ◽

Expiratory Flow

We examined the bronchoconstriction produced by airway hypocapnia in normal subjects. Maximal expiratory flow at 25% vital capacity on partial expiratory flow-volume (PEFV) curves fell during hypocapnia both on air and on an 80% helium- 20% oxygen mixture. Density dependence also fell, suggesting predominantly small airway constriction. The changes seen on PEFV curves were not found on maximal expiratory flow-volume curves, indicating the inhalation to total lung capacity substantially reversed the constriction. Pretreatment with a beta-sympathomimetic agent blocked the response, whereas atropine pretreatment did not, suggesting that hypocapnia affects airway smooth muscle directly, not via cholinergic efferents.

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