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Human Neutrophil Peptides: A Novel Agonist of Platelet Activation and Aggregation

INTRODUCTION: Platelets are involved in the inflammatory and thrombotic complications associated with atherosclerosis. Human neutrophil peptides (HNP), released from activated neutrophils, demonstrate inflammatory effects related to lesion development. HNP bind the low-density lipoprotein receptor (LR) family member LRP1 and LRP8 is the only member on platelets.
HYPOTHESIS: HNP enhance platelet activation and aggregation through interactions with LRP8.
METHODS: Platelet activation and aggregation in response to HNP were determined using flow cytometry and aggregometry. Activation was also examined in the presence of recombinant LRP8 and in LRP8 knockout platelets.
RESULTS: HNP activate platelets as determined by P-selectin expression and the formation of microparticles. HNP sensitize platelets enhancing their aggregatory response to ADP. Lastly, LRP8 plays a role in HNP-induced platelet activation.
CONCLUSIONS: With an improved understanding of the mechanism by which HNP induce platelet activation, we may be able to devise therapeutic strategies to treat patients with cardiovascular diseases.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/18343
Date26 January 2010
CreatorsHenriques, Melanie Dawn
ContributorsZhang, Haibo
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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