High density lipoprotein (HDL) binds lipopolysaccharide (LPS or endotoxin) and neutralizes its toxicity.We investigated the function ofApolipoprotein A-I (ApoA-I),a major apolipoprotein in HDL,in this process.Mouse macrophages were incubated with LPS,LPS+ApoA-I,LPS+ApoA-I+LFF (lipoprotein-free plasma fraction d>1.210 g/ml),LPS+HDL,LPS+HDL+LFF,respectively.MTT method was used to detect the mortality of L-929 cells which were attacked by the release-out cytokines in LPS-activated macrophages.It was found that ApoA-I significantly decreased L-929 cells mortality caused by LPS treatment (LPS vs.LPS+ApoA-I,P<0.05) and this effect became even more significant when LFF was utilized (LPS vs.LPS+ApoA-I+LFF,P<0.01;LPS vs.LPS+HDL+LFF,P<0.01).There was no significant difference between LPS+ApoA-I+LFF and LPS+HDL+LFF treatment,indicating that ApoA-I was the main factor.We also investigated in vivo effects of ApoA-I on mouse mortality rate and survival time after LPS administration.We found that the mortality in LPS+ApoA-I group (20%) and in LPS+ApoA-I+LFF group (10%) was significantly lower than that in LPS group (80%) (P<0.05,P<0.01,respectively);the survival time was (43.20 +10.13) h in LPS+Apc A-I group and (46.80 + 3.79) h in LPS+ApoA-I+LFF group,which were significantly longer than that in LPS group (16.25 ± 17.28) h (P<0.01).We also carried out in vitro binding study to investigate the binding capacity of ApoA-I and ApoA-I+LFF to fluorescence labeled LPS (FITC-LPS).It was shown that both ApoA-I and ApoA-I+LFF could bind with FITC-LPS,however,the binding capacity of ApoA-I+LFF to FITC-LPS (64.47 + 8.06) was significantly higher than that of ApoA-I alone (24.35 ± 3.70)(P<0.01).The results suggest that: (1) ApoA-I has the ability to bind with and protect against LPS;(2) LFF enhances the effect of ApoA-I;(3) ApoA-I is the major contributor for HDL anti-endotoxin function.