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Platelet hyaluronidase-2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation

Sami Albeiroti, Katayoun Ayasoufi, David R. Hill, Bo Shen and Carol A. de la Motte

Key points

  • Platelet HYAL2 is stored in α-granules and becomes surface expressed upon activation, where it functions to degrade extracellular matrix.

  • Platelets from IBD patients contain lower HYAL2 protein and activity than non-IBD controls.

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 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). 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 pro-inflammatory 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 evidence that patients with IBD have lower platelet HYAL2 levels and activity than healthy controls.

  • Submitted July 22, 2014.
  • Accepted November 7, 2014.