• Saskia Braber, Marco Thio, Bart R Blokhuis, Paul A J Henricks, Pim J Koelink, Tom Groot Kormelink, Gillina F G Bezemer, Huib A M Kerstjens, Dirkje S Postma, Johan Garssen, Aletta D Kraneveld, Frank A Redegeld, and Gert Folkerts.
• Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands. s.braber@uu.nl
• Am. J. Respir. Crit. Care Med.. 2012 Apr 15;185(8):817-24.

RationaleNeutrophils 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 free light chains (IgLC) are able to prolong the life of neutrophils; therefore, IgLC may contribute to the chronic state of inflammation.ObjectivesIn this study, the relation between IgLC and COPD has been investigated.MethodsWe 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 ResultsIncreased 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, IgLC bound to 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.ConclusionsThis study describes for the first time an association between neutrophils and IgLC in the pathophysiology of COPD, which could open new avenues to targeted treatment of this chronic disease.

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