Cell adhesion molecules and the bronchial epithelium

We thank Professor David Garrod, Dr.Tom Fleming, Dr. Dorian Haskard, and Professor Tak Lee for supplying some of the antibodies used in our studies.The bronchial epithelium is the major barrier between the host and the provoking antigens in bronchial asthma. Recent studies have indicated that the epithelium is a truly stratified structure, with the superficial columnar cells depending on the underlying basal cells for anchorage. Only columnar cells are shed into bronchial lavage fluid. The epithelium is more fragile in asthma and more cells are lost in clusters. Desmosomes appear to be the major structural adhesion mechanism at the plane of cleavage between the columnar cells and the basal cells. The as- and 134-integrins, which contribute to hemidesmosomes and anchor cells to the underlying basement membrane, are expressed solely by basal cells. The apical aspects of the columnar cells are sealed by tight and intermediate junctions. There is constitutive expression of ICAM-1 and E-selectin in the vasculature of the bronchial mucosa, and ICAM is also present within the epithelium. These findings indicate that the bronchial epithelium is a complex structure that, as a mucosal surface, has constitutive expression of inflammatory cell adhesion molecules to serve normal leukocyte traffic.peer-reviewe

Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response

Rhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-?, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-?(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-? antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-?(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-? on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-? and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-? contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3

The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects

Attention has recently been focused on the basal cells of the tracheobronchial epithelium as the mechanism of anchorage of the tall columnar cells, which themselves do not appear to form hemidesmosomes with the basement membrane of the epithelium. Residual basal cells have been described as remaining attached to the basement membrane after epithelial denudation. This led this group to formulate the hypothesis that there may be a potential plane of cleavage between the basal cells and the overlying columnar cell layer within the bronchial epithelium, which becomes disrupted in asthma.peer-reviewe

Human bronchial fibroblasts express the 5-lipoxygenase pathway

BACKGROUND: Fibroblasts are implicated in sub-epithelial fibrosis in remodeled asthmatic airways and contribute to airway inflammation by releasing cytokines and other mediators. Fibroblast activity is influenced by members of the leukotriene family of bronchoconstrictor and inflammatory mediators, but it is not known whether human bronchial fibroblasts can synthesize leukotrienes. METHODS: The expression of leukotriene biosynthetic enzymes and receptors was investigated in primary fibroblasts from the bronchi of normal and asthmatic adult subjects using RT-PCR, Western blotting, immunocytochemistry and flow cytometry. RESULTS: These techniques revealed that human bronchial fibroblasts from both subject groups constitutively express 5-lipoxygenase, its activating protein FLAP, the terminal enzymes leukotriene A(4 )hydrolase and leukotriene C(4 )synthase, and receptors for leukotriene B(4 )(BLT1) and cysteinyl-leukotrienes (CysLT(1)). Human bronchial fibroblasts generated immunoreactive leukotriene B(4 )and cysteinyl-leukotrienes spontaneously and in increased amounts after calcium-dependent activation. Flow cytometry showed that human bronchial fibroblasts transformed to a myofibroblast-like phenotype by culture with transforming growth factor-β(1 )expressed 320–400% more immunofluorescence for leukotriene C(4 )synthase and CysLT(1 )receptors, with 60–80% reductions in leukotriene A(4 )hydrolase and BLT1 receptors. CONCLUSION: These results indicate that human bronchial fibroblasts may not only respond to exogenous leukotrienes but also generate leukotrienes implicated in narrowing, inflammation and remodeling of the asthmatic airway

The temporal relationship between the neural and vascular actions of kallidin within the nose

The time course of effect of the B2-receptor agonist kallidin (K) on induced changes of nasal airflow, rhinorrhoea, nasal pain, sneezing and nasal microvascular leakage has been examined and compared with its B2 metabolite agonist bradykinin (B) and the B1-agonist [des-arg9]-bradykinin (D). When administered as a single dose K and B induced an immediate sensation of pain, rhinorrhoea, elevations in lavage albumin and protein levels and a sustained increase in nasal airways resistance (NAR) for 5–40 min post-challenge. [des-arg9]-Bradykinin and vehicle placebo (V) were without effect on any of these indices. These studies identify the action of K and B within the nose and differentiate the neural and vascular effects of these kinins in addition to suggesting the potential that nasal blockage and nasal microvascular leakage represent alterations in differing vascular compartments. These findings have implications for the understanding and therapeutic manipulation of rhinitis

Highly porous flame-retardant and sustainable biofoams based on wheat gluten and in situ polymerized silica

Wheat gluten from ethanol production is presented as flame-retardant silica hybrid biofoams for insulation. The porosity of 90% and self-extinguishing nature make them an attractive alternative to petroleum-based foams.</p