Role of neutrophil elastase in hypersecretion in asthma

Abstract

Goblet cell (GC) hyperplasia and mucous plugging are common in patients with acute asthma. These patients also show neutrophil recruitment into the airways. Neutrophils contain elastase, a potent secretagogue in airways. Therefore, it was reasoned that neutrophil recruitment, by releasing elastase, could result in GC hypersecretion. When neutrophil chemoattractants were instilled in the airways of guinea-pigs, time-dependent neutrophil recruitment and GC degranulation occurred. An inhibitor of leukocyte infiltration (NP15669) prevented both responses, implicating neutrophils. An inhibitor of neutrophil elastase (ICI 200,355) abolished GC degranulation, implicating elastase. Further studies implicate movement of elastase from cytoplasmic granules to the neutrophil surface, and they suggest a role for adhesion molecules on neutrophils and on GCs in neutrophil-dependent GC degranulation. Similarly, instillation of ovalbumin (OVA) into airways of OVA-sensitized guinea-pigs caused early recruitment of neutrophils and GC degranulation. GC degranulation was prevented by pretreatment with NP15669 or ICI 200,355. These results implicate neutrophil release of elastase in allergen-induced hypersecretion. The results suggest a mechanism for the mucous plugging that occurs in acute asthma; prevention of neutrophil recruitment, prevention of neutrophil-GC adhesion, or inhibition of elastase activity could provide effective therapy for this serious pathophysiological abnormality. Eur Respir J 1999; 13: 190±196.

LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells

“…Therefore, decreased neutrophil numbers in the BAL may be a direct result of reduced availability of neutrophils in circulation. Neutrophil elastase is a known inducer of mucin expression and MCM (22,40). However, the decrease in neutrophils in BAL was not accompanied with significant reduction of MCM.…”

Neutrophilic airway inflammation and IL‐17

“…Elastase released from neutrophils is a very potent secretagogue in airway gland cells (32,33). In addition, this specific indicator of neutrophil activity can cause bronchial hyperresponsiveness and tissue remodelling in A. LindØn 1 , M. Adachi rodent airways in vivo and in collagen gels in vitro (34)(35)(36)(37)(38), thus providing additional evidence for functional impact of neutrophils in the airways and lungs.…”

Inhibition of neutrophil elastase-induced goblet cell metaplasia by tiotropium in mice

“…Neutrophil elastase (NE) is a serine protease that stimulates mucus secretion [3], and its level is increased in the sputum with nanomolar or micromolar concentrations in chronic bronchitis [4]. NE is generally used for an animal model of emphysema, based on the hypothesis that COPD is caused by an imbalance between protease activity and antiprotease activity.…”