High-density lipoproteins (HDL) inhibit endotoxin-induced leukocyte adhesion on endothelial cells in rats: effect of the acute-phase HDL.

High-density lipoprotein (HDL) plays an important role not only in protecting against atherosclerosis but also in innate immunity. Several lines of evidence showed that HDL could ameliorate the toxic effects of endotoxin or lipopolysaccharide (LPS). In this study, we examined whether HDL could inhibit LPS-induced leukocyte adhesion on endothelial cells in rats. Normal HDL and acute-phase HDL (AP-HDL) were purified from plasma of hamsters that received normal saline and LPS injection, respectively. Wistar rats were given LPS injection and the number of leukocytes adhering to endothelial cells of the mesenteric venules was determined using intravital fluorescence videomicroscopy. Intravenous injection of LPS enhanced leukocyte adhesion to the mesenteric venules. However, when LPS was preincubated with normal HDL, leukocyte adhesion on endothelial cells in response to LPS was significantly attenuated in a dose-dependent manner. AP-HDL was also able to significantly decrease LPS-induced leukocyte adhesion on endothelial cells. It appeared to be more effective than normal HDL since lower concentrations were required. This inhibitory effect of HDL was not due to HDL itself but it requires preincubation of HDL with LPS. When HDL was separated into protein and lipid fractions, it was found that lipid-free apoHDL was able to significantly inhibit LPS-induced leukocyte adhesion, whereas lipid component of HDL had no effect. In conclusion, HDL, both normal and acute-phase, could inhibit an inflammatory effect of LPS on endothelial cells in vivo. AP-HDL was more potent than normal HDL in inhibiting LPS-induced leukocyte adhesion, and this effect was attributed to the protein component of HDL.