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Biomedical subjects

S Montefort

Publications and source records attributed to S Montefort.

29 records · Page 2Linked to original sources
PubMed1993

Leucocyte-endothelial adhesion molecules and their role in bronchial asthma and allergic rhinitis.

Leucocyte-endothelial adhesion molecules are involved in the initial stages of the recruitment and migration of inflammatory leucocytes from the circulation to sites of inflammation. There is accumulating evidence for their involvement in the pathophysiology of airway mucosal allergic inflammation, such as that found in asthma and rhinitis. The best characterized adhesion molecule families are the integrins, the immunoglobulin supergene family and the selectins. This review article describes some of the characteristics and properties of these families. We also discuss the situations in which these adhesion molecules might be involved in inflammatory airway diseases, and how evidence for this role might lead to future modes of therapy for these common conditions.

Asthma↗
PubMed1993

The distribution of adhesive mechanisms in the normal bronchial epithelium.

The integrity of the bronchial epithelium is dependent on various adhesion mechanisms that serve to hold the composite structure of the epithelium together and anchor it to the underlying basement membrane. Using immunohistochemistry we wanted to map out a number of these junctional and non-junctional adhesion mechanisms in the normal human bronchial epithelium. The beta 1-associated integrin subunit alpha 2 was immunolocalized to all of the epithelial intercellular spaces, whilst alpha 6 and beta 4 were strongly evident at the basal cell layer basement membrane junction. The alpha 1 and alpha 5 integrin subunits were not detected anywhere in the epithelium. Monoclonal antibodies (MoAbs) to tight junction polypeptides and the E-cadherin, liver cell adhesion molecule (LCAM), immunolocalized to the apicolateral portions of the intercellular junctions between all neighbouring columnar cells, with LCAM extending further along the lateral cell membrane. Desmosomal protein (dp) 1 and 2 MoAbs gave a punctate pattern between all of the suprabasal cells, and exhibited the greatest intensity of staining at the junction between the columnar and basal cell layers. In conclusion, there is an organized distribution of adhesive mechanisms within the normal human bronchial epithelium, which may be targeted by the various insults which lead to epithelial shedding.

Antibodies, Monoclonal↗
PubMed1993

Investigative use of fibreoptic bronchoscopy for local airway challenge in asthma.

Local airway challenge has advantages over inhalation bronchial challenge as the response of the airway can be restricted and directly observed. It has been safely performed in subjects with mild or moderate asthma, either by the direct instillation of challenge solution to the selected segmental airways via a bronchoscope, or delivered to an airway segment isolated with a double-balloon catheter. However, these techniques carry potential complications, such as generalized wheeze, and due care is required in selection of subjects. Most investigators have used the method for studying the airway events following allergen challenge. Others have studied the airway changes following challenge with non-allergen provocation agents, such as hypertonic saline, adenosine 5'-monophosphate and cold dry air. The method has helped to define changes in the inflammatory cells and mediators in relation to early and late airway responses to allergen. Similarly, study of airway events following local challenge with hypertonic solution has provided useful knowledge in understanding the mechanisms of exercise-induced asthma. With more experience and an improved margin of safety, it will be possible to study local changes in airway physiology following local airway challenge. Finally, the techniques also have potential use for studying the airway events following provocation with a wide range of agents of potential relevance to the pathogenesis of asthma.

Allergens↗
PubMed1992

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

BACKGROUND: 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. METHODS: Bronchoalveolar lavage samples were obtained during bronchoscopy from eight patients with atopic asthma and four normal controls. Ultrathin sections of lavage cell pellets were examined by electron microscopy and the number of columnar and basal cells found in each epithelial cell cluster was counted. Cytocentrifuge preparations of the lavage samples from the same subjects were also examined for free epithelial cells and epithelial cell clusters. RESULTS: Electron microscopic examination of the cell pellets showed that basal cells were present in very small numbers in the epithelial clusters in all subjects (mean 0.03 (SE 0.02)/cluster) and the ratio of columnar cells to basal cells was far greater than was encountered in the intact bronchial epithelium (167 nu 4). The cytocentrifuge preparations showed an increased number of epithelial cell clusters and epithelial cells in the asthmatic patients. Although these clusters were similar in size in the two groups of subjects (6.3 nu 5.1 cells/cluster) the ratio of free epithelial cells to cells within the cluster was higher in the non-asthmatic subjects. CONCLUSIONS: It is proposed that shedding of epithelial cells occurs along a suprabasal plane and that there is a potential plane of cleavage between the suprabasal and the basal cell layers, which might be more vulnerable to the various insults.

Adult↗
PubMed1992

The expression of leukocyte-endothelial adhesion molecules is increased in perennial allergic rhinitis.

Accumulating evidence supports the importance of leukocyte-endothelial cell adhesion molecule (CAM) expression as an initiating process in tissue inflammation. To investigate the relevance of CAM expression to allergic airways inflammation, nasal biopsies from patients with perennial allergic rhinitis (n = 8) and from nonatopic healthy volunteers (n = 8) were immunostained with monoclonal antibodies directed against the CAMs, intercellular adhesion molecule-1 (ICAM-1), endothelial cell adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). The endothelial staining of these CAMs was related to the number of vessels within each biopsy, delineated by a monoclonal antibody against Ulex europaeus-1 lectin bound to endothelial cells, and to the number of tissue leukocytes staining for one of the ligands of ICAM-1, the beta 2 integrin, lymphocyte function-associated antigen (LFA-1). Expression of CAMs was related to the number of infiltrating neutrophils, eosinophils, and lymphocytes identified immunohistochemically within the biopsies. ICAM-1 was the most prominent CAM present on the endothelium of the normal nasal mucosa, with less expression of ELAM-1 and only minimal or absent expression of VCAM-1. In perennial rhinitis, both ICAM-1 (P less than 0.05) and VCAM-1 (P less than 0.01) expression on endothelial cells were increased and were positively correlated in their level of expression (P less than 0.002). The number of tissue LFA-1-positive cells was significantly greater (P less than 0.05) in the biopsies from the perennial rhinitics (median, 27.3/mm2) than from the healthy controls (median, 5.3 cells/mm2). LFA-1 expression significantly correlated with the number of ICAM-1-positive vessels (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects.

Bronchial lavage and biopsy studies suggest the involvement of eosinophils and T-lymphocytes in allergic inflammation in asthma. There is evidence suggesting that the expression of adhesion molecules on endothelial cells and of their receptors on leucocytes is involved in this process. To investigate these mechanisms we have obtained bronchial mucosal biopsies from 10 normal subjects and from 10 symptomatic atopic asthmatics. Six of the asthmatics were re-biopsied after 6 weeks of inhaled beclomethasone dipropionate (BDP) during which time their clinical response was monitored. Frozen sections were stained by the immunoperoxidase method using monoclonal antibody (MoAb) 6.5B5 to identify expression of intercellular adhesion molecule (ICAM-1) and MoAb 1.2B6 for endothelial leucocyte adhesion molecule (ELAM-1). Araldite-embedded sections were also stained for eosinophils using MoAb EG2 to identify eosinophilic cationic protein (ECP). A significant mucosal eosinophilia was apparent in the asthmatic but not in the normal biopsies. Immunostaining for ICAM-1 was observed in both the epithelium and endothelium and ELAM-1 in endothelium, with no significant differences being apparent between the asthmatic and normal subjects. Topical BDP markedly reduced the mucosal eosinophilia without affecting the expression of either adhesion molecule. Using this method, we conclude that there is basal expression of ICAM-1 and ELAM-1 in normal human bronchial mucosa, which is not significantly different from that in asthmatics, and that it is insensitive to suppression with corticosteroids at an inhaled dose that causes clinical improvement.

Adult↗