Abstract 5869: HDL and ApoA-I Attenuate Neutrophil Activation in in vitro and in vivo Models of Inflammation: A Role for Lipid Rafts
HDL is a well recognized cardioprotective particle; plasma levels of HDL correlate inversely with progression of atherosclerosis. An important function of HDL is its role in regulating inflammation, particularly that associated with innate immune response. However the mechanisms remain poorly understood. In the current study, CD11b was measured on human neutrophils as a marker of neutrophil activation. Neutrophil activation was significantly attenuated after only a 15min incubation with apoA-I, while suppression of CD11b was only evident after 60mins incubation with HDL. We also determined that neutrophils express ABCA1, a transporter required for inhibition of CD11b activation by apoA-I. When examining cholesterol content of non-ordered membrane regions, HDL, but not apoA-I removed significant amount of cholesterol from these regions. However apoA-I significantly and rapidly reduced lipid raft content while HDL did this slower and to a lesser extent. There was a strong correlation between lipid raft abundance and CD11b activation but not with cholesterol removal from non-ordered regions. We also show for the first time that apoA-I can inhibit leukocyte recruitment in an acute model of inflammation using intravital microscopy. Further, we confirmed that infusion of rHDL in patients with peripheral vascular disease significantly attenuates circulating neutrophil activation. Thus we have described a novel role for HDL in regulating the innate immune system by inhibiting neutrophil activation both in vitro and in vivo. We propose that anti-inflammatory effects of HDL and apoA-I involves a mechanism requiring changes in cellular lipid raft content.