Asthma: a dynamic disease of inflammation and repair.
It is now widely accepted that asthma in its varied forms is an inflammatory disorder of the airways in which mediator release from activated mast cells and eosinophils plays a major role. T lymphocytes take a primary role in orchestrating these processes through their capacity to generate a range of cytokines of the interleukin 4 gene cluster encoded on the long arm of chromosome 5. Additional cytokines derived from mast cells and eosinophils also play a key role, especially tumour necrosis factor alpha, which is responsible for initiating the up-regulation of vascular adhesion molecules involved in the recruitment of eosinophils and other inflammatory cells from the circulation. The importance of C-X-C and C-C chemokines as local chemoattractants and activating stimuli is also recognized. In addition to releasing an array of pharmacologically active autacoids, the inflammatory response in asthma results in the generation of proteolytic activities from mast cells (tryptase, chymase), eosinophils (MMP-9) and the epithelium itself (MMP-2, MMP-9), which exert tissue-destructive and cell-signalling effects. The epithelium is also highly activated, as evidenced by the up-regulation of cytokine production, inducible enzymes and soluble mediators. Increased surface expression of the epithelial isoform of CD44 (9v) and subepithelial proliferation of myofibroblasts are indicative of a simultaneous active repair process and the laying down of new interstitial collagens. Together, inflammatory and repair processes create the complex phenotype that characterizes asthma and its progression.
Holgate
S T
ST
School of Medicine, University of Southampton, Southampton General Hospital, UK.
D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000276:immunology; D002908:Chronic Disease; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology
D007073:Immunoglobulin E