Expression of CD44 and integrins in bronchial mucosa of normal and mildly asthmatic subjects

Abstract

E Ex xp pr re es ss si io on n o of f C CD D4 44 4 a an nd d i in nt te eg gr ri in ns s i in n b br ro on nc ch hi ia al l m mu uc co os sa a o of f n no or rm ma al l a an nd d m mi il ld dl ly y a as st th hm ma at ti ic c s su ub bj je ec ct ts s Significantly increased numbers of eosinophils (p<0.01) were evident in the bronchial submucosa of asthmatic subjects. In epithelium there were more CD44+ (p<0.02) and lymphocyte function-associated antigen-1 (LFA-1)+ (p<0.06) leucocytes in asthmatics than in normal subjects. Bronchial epithelial cells stained positively with anti-CD44 monoclonal antibodies (moAb) in both groups; however, when the staining was expressed as percentage of the total basement membrane, a considerable and highly significant increase was observed in the asthmatics (median 80 vs 22%, p=0.003). Few leucocytes were positive for very late activation antigen (VLA)-1, VLA-2 and VLA-4. The moAb for VLA-6 stained the basement membrane of the bronchial epithelium; while intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were constitutively expressed in endothelium. A positive correlation was found between LFA-1+ cells and activated eosinophils (EG2+) in the submucosa (p<0.005; r s =0.80).We conclude that even in mild asthma there is evidence of increased expression of cell surface ligands, and suggest that adhesive mechanisms play a role both in cell recruitment and disease activity.

Consistent Biomarkers and Related Pathogenesis Underlying Asthma Revealed by Systems Biology Approach

“…Within this network, CD44 encoding a cell surface adhesion receptor was the most highly ranked hub gene (degree = 59). A previous study showed that CD44 was significantly up-regulated in the bronchial epithelium in asthmatics compared with the controls [42]. Higher expression of CD44 in blood eosinophils could regulate the recruitment and function of leukocytes in asthmatics and are considered as a marker of bronchial asthma [43].…”

Hyaluronan and Layilin Mediate Loss of Airway Epithelial Barrier Function Induced by Cigarette Smoke by Decreasing E-cadherin

“…What pointed toward layilin as an ideal HA receptor to be involved epithelial permeability is that it is known to interact with members of the ezrin, radixin, and moesin proteins (81) that are key regulators of cytoskeletonplasma membrane interactions in polarized cell. CD44 and RHAMM are two of the better characterized HA receptors in airway epithelial cells (19,21,(82)(83)(84), but in intact epithelium CD44 expression is restricted to the basolateral domain (83,85,86) and thus, at least initially, cannot be accessed by fragments released during luminal HA degradation. RHAMM is apically expressed (19,21) but lacks a cytoplasmic domain.…”

Fluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects

“…Persistent repair mechanisms are also implicated in airway remodeling [ 40 , 41 ]. These include upregulation of cyclin-dependent kinase inhibitor, p21 (waf) [ 42 ], EGFR [ 43 ] and CD-44 [ 44 , 45 ]. In asthma, epithelial shedding is largely attributed to the induction of apoptosis in AECs by infiltrating T cells and eosinophils along with increased pro-inflammatory cytokines including IFN-gamma and TNF-alpha [ 46 ].…”