title: Platelet hyaluronidase-2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation.
abstract: Following injury, platelets rapidly interact with the exposed extracellular matrix (ECM) of the vessel wall and the surrounding tissues. Hyaluronan (HA) is a major glycosaminoglycan component of the ECM and plays a significant role in regulating inflammation. We have recently reported that human platelets degrade HA from the surfaces of activated endothelial cells into fragments capable of inducing immune responses by monocytes. We also showed that human platelets contain the enzyme hyaluronidase-2 (HYAL2), one of two major hyaluronidases that digest HA in somatic tissues. The deposition of HA increases in inflamed tissues in several inflammatory diseases, including inflammatory bowel disease (IBD). We therefore wanted to define the mechanism by which platelets degrade HA in the inflamed tissues. In this study, we show that human platelets degrade the proinflammatory matrix HA through the activity of HYAL2 and that platelet activation causes the immediate translocation of HYAL2 from a distinct population of α-granules to platelet surfaces where it exerts its catalytic activity. Finally, we show that patients with IBD have lower platelet HYAL2 levels and activity than healthy controls.
authors.affiliation: Department of Pathobiology, Cleveland Clinic Lerner Research Institute, Cleveland, OH; Department of Chemistry, Cleveland State University, Cleveland, OH;
authors.forename: Sami
authors.initials: S
authors.lastname: Albeiroti
authors.affiliation: Department of Immunology, Cleveland Clinic Lerner Research Institute, Cleveland, OH;
authors.forename: Katayoun
authors.initials: K
authors.lastname: Ayasoufi
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI; and.
authors.forename: David R
authors.initials: DR
authors.lastname: Hill
authors.affiliation: Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH.
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Pathobiology, Cleveland Clinic Lerner Research Institute, Cleveland, OH;
authors.forename: Carol A
authors.initials: CA
authors.lastname: de la Motte
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D015539:Platelet Activation; D011379:Prognosis; D021381:Protein Transport
chemical_list: D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D006820:Hyaluronic Acid; C473096:Hyal2 protein, human; D006821:Hyaluronoglucosaminidase