Granzyme K: a novel mediator in acute airway inflammation

Abstract

Background: Granzymes are a sub-family of serine proteases involved in the pathogenesis of many inflammatory disorders. In contrast to granzyme A and B, the role of granzyme K (GrK) in human lung diseases is unknown. Therefore, we investigated the release and expression of GrK in allergic asthma, chronic obstructive pulmonary disease (COPD), and bronchopneumonia.

Methods: Soluble GrK was quantified using an enzyme-linked immunosorbent assay in bronchoalveolar lavage fluid of patients with allergic asthma (before and after segmental allergen challenge), and patients with mild COPD, pneumonia, and healthy controls. The molecular form of GrK was analyzed by Western blot. Flow-cytometry was performed to determine the cellular expression of GrK.

Results: Compared with healthy controls, there were normal levels of soluble GrK in bronchoalveolar lavage fluid of patients with COPD, and patients with allergic asthma before allergen challenge. In contrast, soluble GrK was strongly increased in bronchoalveolar lavage fluid of patients with acute bronchopneumonia. In patients with allergic asthma, there was a significant increase in soluble GrK as well as in GrK expressing CD8+ T cells in bronchoalveolar lavage fluid 24 hours and 72 hours after allergen challenge. After allergen challenge, soluble GrK correlated with the percentage of GrK expressing CD8+ T cells. Finally, we show that the endobronchial release of the CCR5 ligand CCL3 might be a mechanism for the recruitment of GrK+CD8+ T cells after allergen challenge.

Conclusion: These data provide first evidence that the expression of GrK is upregulated in acute airway inflammation, both in infectious and non-infectious diseases.