Lactosyl derivatives function in a rat model of severe burn shock by acting as antagonists against CD11b of integrin on leukocytes.
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.
Zhao
Zhihui
Z
Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, China.
Li
Qing
Q
Hu
Jiale
J
Li
Zhongjun
Z
Liu
Jinghua
J
Liu
Aihua
A
Deng
Peng
P
Zhang
Lin
L
Gong
Xiaowei
X
Zhao
Kesen
K
Zhang
Shuangquan
S
Jiang
Yong
Y
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
C540503:An-2 compound; D039481:CD11b Antigen; C540504:Gu-4 compound; D009844:Oligosaccharides; D011412:Propanolamines; D005973:Glutamine; D007785:Lactose