Published ahead of print on November 3, 2003, doi:10.1164/rccm.200305-619OC
© 2004 American Thoracic Society Free Secretory Component from Cystic Fibrosis Sputa Displays the Cystic Fibrosis Glycosylation PhenotypeSchool of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, and Department of Respiratory Paediatrics, Royal Brompton Hospital, London, United Kingdom Correspondence and requests for reprints should be addressed to Lindsay J. Marshall, Ph.D., School of Pharmacy and Biomedical Sciences, St. Michael's Building, White Swan Road, University of Portsmouth, Portsmouth PO1 2DT, UK. E-mail: lindsay.marshall{at}port.ac.uk Secretory IgA contributes to humoral defense mechanisms against pathogens targeting mucosal surfaces, and secretory component (SC) fulfills multiple roles in this defense. The aims of this study were to quantify total SC and to analyze the form of free SC in sputa from normal subjects, subjects with asthma, and subjects with cystic fibrosis (CF). Significantly higher levels of SC were detected in CF compared with both other groups. Gel filtration chromatography revealed that SC in CF was relatively degraded. Free SC normally binds interleukin (IL)-8 and inhibits its function. However, in CF sputa, IL-8 binding to intact SC was reduced. Analysis of the total carbohydrate content of free SC signified overglycosylation in CF compared with normal subjects and subjects with asthma. Monosaccharide composition analysis of free SC from CF subjects revealed overfucosylation and undersialylation, in agreement with the reported CF glycosylation phenotype. SC binding to IL-8 did not interfere with the binding of IL-8 to heparin, indicating distinct binding sites on IL-8 for negative regulation of function by SC and heparin. We suggest that defective structure and function of SC contribute to the characteristic sustained inflammatory response in the CF airways.
Key Words: polymeric immunoglobulin receptor glycoproteins inflammation respiratory mucosa This article has been cited by other articles:
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