Effects of human apolipoprotein A-I on endotoxin-induced leukocyte adhesion on endothelial cells in vivo and on the growth of Escherichia coli in vitro.
BACKGROUND
High-density lipoprotein (HDL) has been shown to inhibit leukocyte adhesion to endothelial cells induced by endotoxin in vivo and suppress the growth of bacteria in vitro; however, the components responsible for these effects, either lipids or proteins, are not yet defined. In this study, we examined the effects of apolipoprotein (apo) A-I, the major protein of HDL, on ameliorating the effect of endotoxin and inhibiting the growth of bacteria.


METHODS
Apo A-I, purified from normal human HDL, was incubated with endotoxin. Leukocyte adhesion to endothelial cells of rat mesenteric venules was assessed using intravital fluorescence microscopy. Ability of apo A-I to inhibit the growth of Escherichia coli was assessed using a spread plate method.


RESULTS
Purified, lipid-free apo A-I could inhibit endotoxin-induced leukocyte adhesion to endothelial cells in vivo in a dose-dependent manner. In addition, apoA-I was able to suppress the growth of Escherichia coli in vitro.


CONCLUSIONS
These data suggest that apo A-I of HDL can directly interact with endotoxin, ameliorating its effect and that apo A-I may have a direct toxic effect on whole bacteria. Therefore, therapeutic use of apo A-I in septicemia and bacterial infection should be further explored.
Thaveeratitham
Premtip
P
Interdepartment of Physiology, Graduate School, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Plengpanich
Wanee
W
Naen-Udorn
Worakamol
W
Patumraj
Suthiluk
S
Khovidhunkit
Weerapan
W
D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D016632:Apolipoprotein A-I; D004338:Drug Combinations; D008070:Lipopolysaccharides