NEW ASPECTS OF ASTHMA PATHOGENESIS

Abstract

Asthma is a chronic, inflammatory disease of the airway characterized by intermittent airflow limitation, airway hyperresponsiveness, presence of activated inflammatory cells and mediators, airway structural changes (remodelling). Airway smooth muscle (ASM) cells actively participate in the remodelling and inflammatory processes through proliferation, release of proinflammatory cytokines, chemokines, and extracellular matrix (ECM) proteins. Eosinophils as essential inflammatory cells may be of importance in ASM remodelling. Eosinophils induce ASM cells proliferation via the secretion of cysteinyl leukotrienes in asthmatics. However there is a possible direct eosinophil-ASM cells functional interaction by adhesion processes. Wingless/integrase-1 (WNT) signaling pathway may be important in the pathogenesis of asthma. The identified WNT-5A is the most abundant WNT ligand with increased expression in asthmatics. It demonstrates that WNT-5A could contribute to remodelling of the airways. Unfortunately, the effect of eosinophil on WNT secretion by ASM cells at present is unknown. Despite the widely acknowledged significance of eosinophils in asthma pathogenesis, the mechanism of eosinophil induced ASM remodelling is unsolved.