An association between neutrophils and immunoglobulin free light chains in the pathogenesis of chronic obstructive pulmonary disease

Rationale: Neutrophils are key players in chronic obstructive pulmonary disease (COPD), and increased numbers of neutrophils are present in sputum and lung tissue of patients with COPD. Interestingly, immunoglobulin freelight chains (IgLC) areable toprolong thelifeofneutrophils; therefore, IgLC may contribute to the chronic state of inflammation. Objectives: In this study, the relation between IgLC and COPD has been investigated. Methods: We investigated the presence of IgLC in different murine lung emphysema models. IgLC levels in serum from mice and patients with COPD were examined by Western blot analysis and ELISA, respectively. IgLC levels in lung tissue were determined by immunohistochemistry. Fluorescence-activated cell sorter and immunofluorescent analysis were used to detect binding between IgLC and human neutrophils. Interleukin-8 (CXCL8) release by neutrophils after IgLC incubation was measured by ELISA. The effect of F991, an IgLC antagonist, was examined on the neutrophil influx in murine lungs after 5 days of smoke exposure. Measurements and Main Results: Increased levels of IgLC in serum of cigarette smoke-exposed and cigarette smoke extract-treated mice compared with control mice were observed. Patients with COPD showed increased serum IgLC and expression of IgLC in lung tissue compared with healthy volunteers. Interestingly, IgLCboundto neutrophils and activated neutrophils to release CXCL8. F991 inhibited the IgLC binding to neutrophils and reduced the smoke-induced neutrophil influx in murine lungs after smoke exposure. Conclusions: This study describes for the first time an association between neutrophils and IgLC in the pathophysiology of COPD, which couldopennewavenues totargetedtreatment of this chronic disease. Copyright © 2012 by the American Thoracic Society.