The role of platelet activation in the expression and function of platelet hyaluronidase‐2 (1046.7)

Abstract

Background: The deposition of hyaluronan (HA), which is a major glycosaminoglycan component of the extracellular matrix, increases during the course of inflammation. The inflammatory HA matrix, which can promote leukocyte binding and recruitment, can be fragmented be the hyaluronidase enzymes, specifically HYAL1 and HYAL2. Our lab has recently shown that human platelets express HYAL2 and that they can degrade HA from the surfaces of intestinal cells into smaller fragments capable of promoting inflammatory cytokine production. Objective: Define the mechanism by which platelets degrade HA and assess the role of platelet activation. Methods: Platelet degradation of purified HA in solution, immobilized HA and cell surface HA was assessed by carbohydrate gel electrophoresis, hyaluronidase assay, and HA ELISA‐like assay, respectively. HYAL2 expression was assessed by immunoblotting and flow cytometry. Results: 1) Platelets degrade purified HA only under acidic pH; 2) Platelets degrade cell surface HA in a HYAL2 dependent manner; 3) Activation of platelets results in increased surface HYAL2 expression and activity; 4) Platelet activation causes an increase in surface expression of HA binding proteins. Significance: Platelets circulate in an activated state during inflammatory diseases. Increased HYAL2 on activated platelets may lead to higher levels of HA fragments that perpetuate inflammation.Grant Funding Source: Supported by the NHLBI