Surfactant protein D deficiency aggravates cigarette smoke-induced lung inflammation

Cigarette smoke (CS) is a main cause of chronic obstructive pulmonary disease. Surfactant protein D (SP-D) regulates host immune defence in the lungs. We investigated the role of SP-D in a murine model of CS-induced pulmonary inflammation.
Wild type and SP-D-deficient mice were exposed to CS for 12 weeks or 3 days. Cell counts and inflammatory cytokine levels in bronchoalveolar lavage fluid were determined. Changes in lipid content were assessed by mass spectrometry. Moreover, the effect of therapeutic administration of recombinant fragment of human SP-D on the acute CS-induced changes was investigated.
In humans, SP-D was upregulated in the lungs of smokers. Moreover, we found that SP-D-deficient mice were more susceptible to CS-induced macrophage-rich airway inflammation. SP-D deficiency influenced local levels of inflammatory cytokines, with increased CCL3 and interleukin-6 but decreased CXCL1. While overall lipid content was higher in SP-D-deficient mice compared to wild type littermates, CS exposure caused significant upregulation of pro-inflammatory ceramides and related ceramide synthase genes in SP-D-deficient mice. Finally, administration of recombinant SP-D alleviated CS-induced macrophage infiltration.
Our results indicate that SP-D deficiency aggravates CS-induced lung inflammation and that recombinant SP-D is a potential therapeutic option for anti-inflammatory treatment of CS-induced pulmonary pathology.