medwireNews: Researchers have found that a protease released by neutrophils degrades a protective airway protein, which could lead to reduced airway defense to bacterial infection and increased risk for acute exacerbations in chronic obstructive pulmonary disease (COPD).
"Our data suggest a new mechanism underlying frequent bacterial infection during [acute exacerbations of] COPD that is characterized by excessive lung inflammation especially neutrophils," say Hong Wei Chu (National Jewish Health, Denver, Colorado, USA) and colleagues.
Their research, published in PLoS One, shows that human neutrophil elastase (HNE) directly degrades recombinant short palate, lung, and nasal epithelium clone 1 (SPLUNC1) - a host defense protein - when the two are incubated at physiologic doses in vitro.
And, in healthy human airway epithelial cells, HNE decreased SPLUNC1 after 4 hours of treatment in a dose-dependent manner, an effect that was sustained for 48 hours afterwards.
This resulted in increased susceptibility to infection; when the cells were infected with nontypeable Haemophilus influenzae (NHTi), those that were incubated with HNE had significantly higher levels of the bacterium in apical supernatants and cells after 48 hours compared with those incubated without HNE.
Treatment with recombinant SPLUNC1 partly reversed the effect of HNE on NHTi infection, significantly reducing levels in apical supernatants by around 43%. Bacterial levels in HNE-treated epithelial cells also declined, but this was not statistically significant, which "suggests that HNE may use other mechanisms to increase bacterial load," note the authors.
To confirm their findings in vivo, Chu and colleagues demonstrated that after 24 hours of intranasal inoculation with NHTi, bacterial load was 30-fold higher in SPLUNC1 knockout mice than wild-type mice.
Furthermore, they found that SPLUNC1 levels were significantly lower in smokers both with (n=4) and without (n=9) COPD compared with healthy nonsmokers (n=5). However, HNE levels were not different in patients with COPD and in those without, which the authors say may be because they examined patients with stable disease. The reduced SPLUNC1 levels in these patients may instead be due to cigarette smoking, they suggest.
"Together, our data suggest that increased HNE, a feature of excessive inflammation during acute exacerbations of COPD and other chronic lung diseases, may contribute to bacterial infections in part through degrading host defense protein SPLUNC1," they conclude.
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