Date of Award

2014

Degree Type

Dissertation

Department

Chemistry

First Advisor

de la Motte, Carol

Subject Headings

Blood platelets -- Immunology, Hyaluronic acid, Inflammatory bowel diseases, Extracellular matrix, Blood-vessels -- Physiology, Biochemistry, biology, immunology, platelets, hyaluronan, hyaluronidase, extracellular matrix

Abstract

Following tissue injury, platelets rapidly interact with the exposed extracellular matrix (ECM) of blood vessel wall and the surrounding tissues. Hyaluronan (HA) is a major polysaccharide component of the ECM and plays a significant role in regulating inflammation. Human platelets can degrade HA from the surfaces of activated endothelial cells into fragments capable of inducing immune responses by monocytes. In addition, platelets contain the enzyme hyaluronidse-2 (HYAL2), one of two major hyaluronidases that digest HA in somatic tissues. The deposition of HA increases in the inflamed tissues in several inflammatory diseases, including Inflammatory Bowel Disease (IBD). This study provides evidence that IBD patients' platelets have low HYAL2 levels and activity and defines the mechanism by which platelets degrade HA in the inflamed tissues. Human platelets degrade the pro-inflammatory matrix HA through the activity of HYAL2. Importantly, platelet activation causes the immediate translocation of HYAL2 from a distinct population of alpha granules to platelet surfaces, where it exerts its catalytic activity. Additionally, platelet activation causes increased binding of platelets to HA. The study also shows that platelets express the novel HA-binding protein KIAA1199, which they release upon activation. Our data provide a new perspective on how platelets interact with their surrounding tissues and explain a possible novel role for platelets in inflammation

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