Free secretory component from cystic fibrosis sputa displays the cystic fibrosis glycosylation phenotype

L. Marshall, B. Perks, K. Bodey, R. Suri, A. Bush, Jan Shute

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)399-406
    Number of pages8
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume169
    Issue number3
    DOIs
    Publication statusPublished - 1 Feb 2004

    Fingerprint

    Dive into the research topics of 'Free secretory component from cystic fibrosis sputa displays the cystic fibrosis glycosylation phenotype'. Together they form a unique fingerprint.

    Cite this