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Human Neutrophil Peptides Mediate Endothelial-Monocyte Interaction, Foam Cell Formation, and Platelet Activation
Quinn, Kieran Henriques, Melanie Tabuchi, Arata Han, Bing Yang, Hong Cheng, Wei-Erh Tole, Soumitra Yu, Hanpo Luo, Alice Charbonney, Emmanuel
Quinn, Kieran
Henriques, Melanie
Tabuchi, Arata
Han, Bing
Yang, Hong
Cheng, Wei-Erh
Tole, Soumitra
Yu, Hanpo
Luo, Alice
Charbonney, Emmanuel
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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.
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Date
2011-09
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American Heart Association
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Quinn_AHA_2011.pdf
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Atherosclerosis, Leukocytes, Transgenic models
Citation
Quinn, K. L., Henriques, M., Tabuchi, A., Han, B., Yang, H., Cheng, W.-E., … Zhang, H. (2011). Human Neutrophil Peptides Mediate Endothelial-Monocyte Interaction, Foam Cell Formation, and Platelet Activation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(9), 2070–2079. http://doi.org/10.1161/ATVBAHA.111.227116