Published ahead of print on November 3, 2003, doi:10.1164/rccm.200305-619OC Am. J. Respir. Crit. Care Med., Volume 169, Number 3, February 2004, 399-406 A more recent version of this article appeared on February 1, 2004
Submitted on May 7, 2003 Free secretory component from cystic fibrosis sputa displays the CF glycosylation phenotypeLindsay J Marshall1*,1 School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom, 2 Respiratory Paediatrics, Royal Brompton Hospital, London, United Kingdom * To whom correspondence should be addressed. E-mail: Lindsay.Marshall{at}port.ac.uk.
Secretory IgA contributes to humoral defence mechanisms against pathogens targeting mucosal surfaces, and secretory component fulfils multiple roles in this defence. The aims of this study were to quantify total secretory component and to analyse the form of free secretory component in sputa from normal, asthmatic and cystic fibrosis subjects. Significantly higher levels of secretory component were detected in cystic fibrosis compared to both other groups. Gel filtration chromatography revealed that secretory component in cystic fibrosis was relatively degraded. Free secretory component normally binds interleukin-8 and inhibits its function. However, in cystic fibrosis sputa, interleukin-8 binding to intact secretory component was reduced. Analysis of the total carbohydrate content of free secretory component signified over-glycosylation in cystic fibrosis compared to normal and asthmatic subjects. Monosaccharide composition analysis of free secretory component from cystic fibrosis subjects revealed over-fucosylation and under-sialylation, in agreement with the reported cystic fibrosis glycosylation phenotype. Secretory component binding to interleukin-8 did not interfere with the binding of interleukin-8 to heparin, indicating distinct binding sites on interleukin-8 for negative regulation of function by secretory component and heparin. We suggest that defective structure and function of secretory component contributes to the characteristic sustained inflammatory response in the cystic fibrosis airways. Key words: polymeric immunoglobulin receptor, glycoproteins, inflammation, respiratory mucosa
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