Role of neutrophils in mucus hypersecretion in COPD and implications for therapy

Treatments in Respiratory Medicine
Suil Kim, J A Nadel

Abstract

Airway mucus hypersecretion is a serious and presently untreatable symptom of COPD. Over the past several years, emerging evidence has implicated epidermal growth factor receptor (EGFR) expression and activation in mucin production by airway epithelial (goblet) cells. Activated neutrophils recruited to the airways (and their secreted products) play several key roles in EGFR-dependent mucus hypersecretion: (i) activated neutrophils secrete tumor necrosis factor (TNF)-alpha, which induces EGFR expression in airway epithelial cells; (ii) activated neutrophils release reactive oxygen species, which activate EGFR; (iii) neutrophil elastase cleaves the EGFR proligand, pro-transforming growth factor (TGF)-alpha, releasing mature TGF alpha which activates EGFR in a ligand-dependent fashion; and (iv) neutrophil elastase causes potent goblet cell degranulation. The secretion of active products by neutrophils appears carefully regulated. The local release of neutrophil elastase requires close contact between the neutrophil and another cell, mediated by surface adhesion molecules, thus limiting proteolysis to the immediate pericellular environment. In the airway lumen, neutrophils undergo apoptosis and are cleared by macrophages without re...Continue Reading

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