Variant size- and glycoforms of the scavenger receptor cysteine-rich protein gp-340 with differential bacterial aggregation |
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Authors: | Christer Eriksson Lars Frängsmyr Liza Danielsson Niemi Vuokko Loimaranta Ulf Holmskov Tomas Bergman Hakon Leffler Howard F Jenkinson Nicklas Strömberg |
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Institution: | 1. Department of Odontology/Cariology, Ume? University, SE 901 87, Ume?, Sweden 2. Medical Biotechnology Institute, University of Southern Denmark, DK-5000, Odense C, Denmark 3. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77, Stockholm, Sweden 4. Department of Molecular Medicine, Lund University, SE-221 00, Lund, Sweden 5. Department of Oral and Dental Science, University of Bristol, Bristol, UK
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Abstract: | Glycoprotein gp-340 aggregates bacteria in saliva as part of innate defence at mucosal surfaces. We have detected size- and
glycoforms of gp-340 between human saliva samples (n = 7) and lung gp-340 from a proteinosis patient using antibodies and lectins in Western blots and ELISA measurements. Western
blots of saliva samples, and of gp-340 purified, from the seven donors using a gp-340 specific antibody distinguished four
gp-340 size variants, designated I to IV (n = 2,2,2 and 1). While saliva gp-340 variants I to III had single bands of increasing sizes, variant IV and lung gp-340 had
double bands. Purified I to IV proteins all revealed a N-terminal sequence TGGWIP upon Edman degradation. Moreover, purified
gp-340 from the seven donors and lung gp-340 shared N-glycans, sialylated Galβ1-3GalNAc and (poly)lactosamine structures.
However, the larger size gp-340 grouping II/III (n = 4) and smaller size grouping I/IV correlated with a secretor, Se(+), and a non secretor, Se(−), dependent glycoform of
gp-340, respectively (p = 0.03). The Se(+) glycoforms contained ABH, Leb, Ley and polylactosamine structures, while the Se(−) glycoforms lacked ABH antigens but expressed Lea, Lex and lactosamine structures. By contrast, lung gp-340 completely lacked ABH, Lea/b, Lex/y or sLex structures. Gp-340 and secretor typing of saliva from additional donors (n = 29) showed gp-340 glycoforms I to IV for 6, 16, 4 and 0 donors, respectively, and 3 non-typeable donors, and verified that
gp-340 glycoforms I and II/III correlate with Se(−) and Se(+) phenotypes, respectively (p < 0.0001). The glycoforms of saliva and lung gp-340 mediated differential aggregation of Leb- (Helicobacter pylori), sialylpolylactosamine- (Streptococcus suis) or sialic acid- (Streptococcus mutans) binding bacteria. In conclusion, variant size- and glycoforms of gp-340 are expressed by different individuals and may modulate
the biological properties of gp-340 pertinent to health and disease. |
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Keywords: | Saliva Gp-340 DMBT1 Secretor status Glycoforms |
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