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, according to study results in the peer-reviewed, open-access journal PLoS One.
“Our findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections,” the authors concluded. “SPLUNC1 therapy likely attenuates bacterial infections during acute exacerbations of chronic obstructive pulmonary disease.”
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 reduced bacterial load in HNE-treated airway epithelial cell, but it did not reduce the bacteria to the normal level.
“This suggests that HNE may use other mechanisms to increase bacterial load. Indeed, a previous study demonstrated that HNE increased epithelial permeability,” the authors wrote. “Therefore, it is possible that HNE could increase bacterial binding in part through disrupting epithelial barrier function in our cell culture model. The contribution of HNE-mediated SPLUNC1 reduction versus epithelial barrier disruption to increased bacterial load will be investigated in our future studies.”