Effect of recombinant bactericidal/permeability-increasing protein on endotoxin translocation and lipopolysaccharide-binding protein/CD14 expression in rats after thermal injury.
OBJECTIVE
To investigate the potential mechanisms underlying the in vivo effect of recombinant bactericidal/permeability-increasing protein (rBPI21) on endogenous bacteria or endotoxin translocation and lipopolysaccharide-binding protein/CD14 expression secondary to thermal injury.


METHODS
Prospective, randomized, controlled animal study.


METHODS
College hospital animal research laboratory.


METHODS
Thirty-six male Wistar rats weighing 250-300 g.


METHODS
The rats were anesthetized, and a 35% total body surface area full-thickness burn was created. Animals were randomized to receive treatment with either rBPI21 or the control protein (albumin). rBPI21 (2 mg/kg body wt, BPI group) or a protein control preparation (burn group) in the same dose was administered in an intravenous bolus at 30 mins and 4 hrs after thermal injury. All animals were killed at 12 and 24 hrs postburn (six to ten rats for each interval). In addition, eight rats were taken as normal controls.


RESULTS
Our data showed that treatment with rBPI21 was effective in preventing endotoxin translocation secondary to severe burns. Meanwhile, tissue lipopolysaccharide-binding protein, CD14, and tumor necrosis factor-alpha mRNA expression in various organs were inhibited markedly by rBPI21 secondary to acute insults (p <.05-.01). Furthermore, significant reduction in serum aminoleucine transferase concentrations and elevation in intestinal diamine oxidase activities in the rBPI21-treated group were found compared with controls (p <.05-.01).


CONCLUSIONS
These findings indicate that endotoxin accumulated in local sites after thermal injury can markedly up-regulate lipopolysaccharide-binding protein/CD14 and tumor necrosis factor-alpha mRNA expression in various organs. Meanwhile, up-regulation of lipopolysaccharide-binding protein/CD14 expression would be the major molecular mechanism of increasing sensitivity to endogenous endotoxin response after burns. Early treatment with rBPI21may be effective in attenuating multiple organ damage resulting from gut-origin endotoxin translocation. This might be associated with the down-regulation effects of tissue lipopolysaccharide-binding protein and CD14 gene expression by the use of rBPI21.
Fang
W H
WH
Department of Microbiology and Immunology, Trauma Research Center, Postgraduate Medical College, 304th Hospital, Beijing, People's Republic of China.
Yao
Y M
YM
Shi
Z G
ZG
Yu
Y
Y
Wu
Y
Y
Lu
L R
LR
Sheng
Z Y
ZY
D000209:Acute-Phase Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D018988:Bacterial Translocation / Q000187:drug effects*; D001798:Blood Proteins / Q000494:pharmacology*; D002056:Burns / Q000503:physiopathology*; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism*; D015870:Gene Expression; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009102:Multiple Organ Failure / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C021623:bactericidal permeability increasing protein