The calcium binding protein S100A12 is highly upregulated in the serum and sputum of patients with allergic asthma and is suggested to be a biomarker and pathologic mediator of asthma.
To test the role of S100A12 in mediating airway inflammation in a mouse model of allergic lung inflammation.
Transgenic mice that express human S100A12 and wild type littermates were sensitized and challenged with ovalbumin and assessed for inflammation, lung structure and function.
Following ovalbumin sensitization and challenge, S100A12 transgenic mice showed reduced peribronchial and perivascular inflammation, mucus production and eosinophilia as well as attenuated airway responsiveness to contractile agonist compared to wild type sensitized and challenged animals. This is explained, at least in part, by remodeled airways in S100A12 transgenic mice with thinning of the airway smooth muscle. S100A12 exposure induced Fas expression and activation of caspase 3 in cultured airway smooth muscle cells, suggesting that airway smooth muscle abnormalities observed in S100A12 transgenic mice may be mediated through myocyte apoptosis.
Conclusion and Clinical Relevance
S100A12 is one of the most abundant proteins found in the airways of human asthmatics, and it was postulated that S100A12 could mediate the inflammatory process. Our study shows for the first time that transgenic expression of S100A12 in the lung of mice does not exacerbate lung inflammation in a model of ovalbumin-induced allergic inflammation. We speculate that the high levels of S100/calgranulins found in BALF of asthmatics and of ovalbumin-treated transgenic S100A12 mice do not significantly mediate pulmonary inflammation.