title: Lactosyl derivatives function in a rat model of severe burn shock by acting as antagonists against CD11b of integrin on leukocytes.
abstract: 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.
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhao
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Jiale
authors.initials: J
authors.lastname: Hu
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Li
authors.forename: Jinghua
authors.initials: J
authors.lastname: Liu
authors.forename: Aihua
authors.initials: A
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Deng
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Gong
authors.forename: Kesen
authors.initials: K
authors.lastname: Zhao
authors.forename: Shuangquan
authors.initials: S
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism*; D002448:Cell Adhesion; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005973:Glutamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009844:Oligosaccharides / Q000737:chemistry / Q000627:therapeutic use; D011412:Propanolamines / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: C540503:An-2 compound; D039481:CD11b Antigen; C540504:Gu-4 compound; D009844:Oligosaccharides; D011412:Propanolamines; D005973:Glutamine; D007785:Lactose