title: Human neutrophil peptides mediate endothelial-monocyte interaction, foam cell formation, and platelet activation.
abstract: OBJECTIVE
  Neutrophils are involved in the inflammatory responses during atherosclerosis. Human neutrophil peptides (HNPs) released from activated neutrophils exert immune modulating properties. We hypothesized that HNPs play an important role in neutrophil-mediated inflammatory cardiovascular responses in atherosclerosis.
  
  
  RESULTS
  We examined the role of HNPs in endothelial-leukocyte interaction, platelet activation, and foam cell formation in vitro and in vivo. We demonstrated that stimulation of human coronary artery endothelial cells with clinically relevant concentrations of HNPs resulted in monocyte adhesion and transmigration; induction of oxidative stress in human macrophages, which accelerates foam cell formation; and activation and aggregation of human platelets. The administration of superoxide dismutase or anti-CD36 antibody reduced foam cell formation and cholesterol efflux. Mice deficient in double genes of low-density lipoprotein receptor and low-density lipoprotein receptor-related protein (LRP), and mice deficient in a single gene of LRP8, the only LRP phenotype expressed in platelets, showed reduced leukocyte rolling and decreased platelet aggregation and thrombus formation in response to HNP stimulation.
  
  
  CONCLUSIONS
  HNPs exert proatherosclerotic properties that appear to be mediated through LRP8 signaling pathways, suggesting an important role for HNPs in the development of inflammatory cardiovascular diseases.
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada.
authors.forename: Kieran L
authors.initials: KL
authors.lastname: Quinn
authors.forename: Melanie
authors.initials: M
authors.lastname: Henriques
authors.forename: Arata
authors.initials: A
authors.lastname: Tabuchi
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Wei-Erh
authors.initials: WE
authors.lastname: Cheng
authors.forename: Soumitra
authors.initials: S
authors.lastname: Tole
authors.forename: Hanpo
authors.initials: H
authors.lastname: Yu
authors.forename: Alice
authors.initials: A
authors.lastname: Luo
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Charbonney
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tullis
authors.forename: Alan
authors.initials: A
authors.lastname: Lazarus
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Robinson
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
authors.forename: Blake R
authors.initials: BR
authors.lastname: Peterson
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Kuebler
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology; D002450:Cell Communication; D018925:Chemokines / Q000096:biosynthesis; D042783:Endothelial Cells / Q000502:physiology*; D005487:Foam Cells / Q000502:physiology*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000502:physiology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000502:physiology; D008297:Male; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D018375:Neutrophil Activation; D018384:Oxidative Stress; D015539:Platelet Activation; D010974:Platelet Aggregation; D023084:alpha-Defensins / Q000502:physiology*
chemical_list: D018925:Chemokines; D026502:LDL-Receptor Related Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D023084:alpha-Defensins; C098773:low density lipoprotein receptor-related protein 8