Human neutrophil peptides mediate endothelial-monocyte interaction, foam cell formation, and platelet activation

Authors

Kieran L. Quinn, Keenan Research Centre for Biomedical Science
Melanie Henriques, Keenan Research Centre for Biomedical Science
Arata Tabuchi, Keenan Research Centre for Biomedical Science
Bing Han, Keenan Research Centre for Biomedical Science
Hong Yang, Keenan Research Centre for Biomedical Science
Wei Erh Cheng, Keenan Research Centre for Biomedical Science
Soumitra Tole, Hospital for Sick Children University of TorontoFollow
Hanpo Yu, Keenan Research Centre for Biomedical Science
Alice Luo, Keenan Research Centre for Biomedical Science
Emmanuel Charbonney, Keenan Research Centre for Biomedical Science
Elizabeth Tullis, Keenan Research Centre for Biomedical Science
Alan Lazarus, Keenan Research Centre for Biomedical Science
Lisa A. Robinson, Hospital for Sick Children University of Toronto
Heyu Ni, Keenan Research Centre for Biomedical Science
Blake R. Peterson, University of Kansas
Wolfgang M. Kuebler, Keenan Research Centre for Biomedical Science
Arthur S. Slutsky, Keenan Research Centre for Biomedical Science
Haibo Zhang, Keenan Research Centre for Biomedical Science

Document Type

Article

Publication Date

9-1-2011

Journal

Arteriosclerosis, Thrombosis, and Vascular Biology

Volume

31

Issue

9

First Page

2070

Last Page

2079

URL with Digital Object Identifier

10.1161/ATVBAHA.111.227116

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. Methods and 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. Conclusion-: 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. © 2011 American Heart Association. All rights reserved.