Journal
GLYCOCONJUGATE JOURNAL
Volume 26, Issue 2, Pages 173-188Publisher
SPRINGER
DOI: 10.1007/s10719-008-9174-0
Keywords
Leukocyte-endothelial cell interaction; Adhesion molecule; Oligosaccharide; Integrin; Burn shock
Categories
Funding
- National Key Basic Research Program ( 973 Program) of China [2002CB513005]
- Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) [IRT0731]
- National Natural Science Foundation of China [30670828, 30572151, 20372003, 90713004]
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Severe burn shock remains an unsolved clinical problem with urgent needs to explore novel therapeutic approaches. In this study, the in vivo bioactivity of a series of synthetic lactosyl derivatives ( oligosaccharides) was assessed on rats with burn shock to elucidate the underlying mechanisms. Administration of An-2 and Gu-4, two lactosyl derivatives with di- and tetravalent beta-D-galactopyranosyl(1-4)-beta-D-glucopyranosyl ligands, significantly prolonged the survival time (P<0.05 vs. saline), stabilized blood pressure and ameliorated the injuries to vital organs after burn. Flow chamber assay displayed that An-2 and Gu-4 markedly decreased the adhesion of leukocytes to microvessel endothelial cells. Competitive binding assay showed that a CD11b antibody significantly interrupted the interaction of An-2 and Gu-4 with leukocytes from rats with burn shock. With fluorescent microscopy, we further found that the oligosaccharides were selectively bound to leukocytes and with a colocalization of CD11b on the cell membrane. Interestingly, the lectin domain-deficient form of CD11b failed to bind with An-2 and Gu-4. The results suggest that both An-2 and Gu-4 significantly inhibit the adhesion of leukocytes to endothelial cells by binding to CD11b and thereby exert protective effects on severe burn shock.
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