[Effect of lipid-bound apoA-I cysteine mutants upon lipopolysaccharide-induced endotoxemia in mice].
OBJECTIVE
To determine the anti-inflammatory functions of different cysteine mutants of apolipoprotein A-I recombinant HDLs.


METHODS
The authors reconstituted recombinant HDLs (namely rHDL74, rHDL129, rHDL195 and rHDL228) by mixing wild type or those mutants with dipalmitoyl phosphatidylcholine and examined their in vivo effects upon LPS-induced endotoxemia in mice.


RESULTS
At 24 h post-injection, mice receiving rHDL74 [TNF-alpha: (24 +/- 3) pg/ml; IL-1beta: (45 +/- 5) pg/ml] had a significant decrease of plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) as compared with control mice receiving either saline or rHDLwt [TNF-alpha: (135 +/- 12) pg/ml; IL-1beta: (82 +/- 8) pg/ml, P < 0.05]. Administration of rHDL74 to mice injected with LPS also led to a protection of lung against acute injury and attenuation of endotoxin-induced clinical symptoms in mice as compared with controls injected with LPS only.


CONCLUSIONS
Compared with rHDLwt, rHDL74 exhibits higher anti-inflammation capabilities. And it may be a potential clinical candidate for therapy for endotoxin-induced septic shock.
Miao
Zhi-min
ZM
Gout Laboratory, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.
Lu
Shu-lai
SL
Li
Chang-gui
CG
Zhao
Shi-hua
SH
Yan
Sheng-li
SL
Wang
Yan-gang
YG
Han
Lin
L
Liu
Shi-guo
SG
Chen
Bao-sheng
BS
Wang
Yun-long
YL
D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology*; D019446:Endotoxemia / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050505:Mutant Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016632:Apolipoprotein A-I; D053583:Interleukin-1beta; D008075:Lipoproteins, HDL; D050505:Mutant Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003545:Cysteine