title: Neutrophil activation is attenuated by high-density lipoprotein and apolipoprotein A-I in in vitro and in vivo models of inflammation.
abstract: OBJECTIVE
  Neutrophils play a key role in the immune response but can undesirably exacerbate inflammation. High-density lipoproteins (HDL) are antiinflammatory particles, exerting beneficial cardiovascular influences. We determined whether HDL exerts antiinflammatory effects on neutrophils and explored the mechanisms by which these occur.
  
  
  RESULTS
  CD11b on activated human neutrophils was significantly attenuated by apolipoprotein A-I (apoA-I) and HDL. The effects of apoA-I were mediated via ABCA1, whereas the effects of HDL were via scavenger receptor BI. Both were associated with a reduction in the abundance of lipid rafts, and a strong correlation between raft abundance and CD11b activation was observed. ApoA-I and HDL reduced neutrophil adhesion to a platelet monolayer under shear flow, as well as neutrophil spreading and migration. ApoA-I also inhibited leukocyte recruitment to the endothelium in an acute in vivo model of inflammation. Finally, infusion of reconstituted HDL in patients with peripheral vascular disease was demonstrated to significantly attenuate neutrophil activation.
  
  
  CONCLUSIONS
  We describe here a novel role for HDL and apoA-I in regulating neutrophil activation using in vitro, in vivo, and clinical approaches. We also show that these effects of HDL and apoA-I involve a mechanism requiring changes in membrane domain content rather than in cholesterol efflux per se.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. andrew.murphy@bakeridi.edu.au
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Woollard
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhartoyo
authors.forename: Roslynn A
authors.initials: RA
authors.lastname: Stirzaker
authors.forename: James
authors.initials: J
authors.lastname: Shaw
authors.forename: Dmitri
authors.initials: D
authors.lastname: Sviridov
authors.forename: Jaye P F
authors.initials: JP
authors.lastname: Chin-Dusting
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology*; D039481:CD11b Antigen / Q000032:analysis; D002448:Cell Adhesion; D002465:Cell Movement; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000517:prevention & control; D008075:Lipoproteins, HDL / Q000502:physiology*; D008297:Male; D021962:Membrane Microdomains / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation; D016491:Peripheral Vascular Diseases / Q000276:immunology; D051122:Scavenger Receptors, Class B; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016632:Apolipoprotein A-I; D039481:CD11b Antigen; C509295:ITGAM protein, human; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; D013755:Tetradecanoylphorbol Acetate