Hyal2 is a glycosylphosphatidylinositol-anchored, lipid raft-associated hyaluronidase

André, Bénédicte; Duterme, Cecile; Moer, Kris Van; Mertens-Strijthagen, J.; Jadot, Michel; Flamion, Bruno

doi:10.1016/j.bbrc.2011.06.125

Cited by 51 publications

(43 citation statements)

References 26 publications

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“…We also demonstrate that platelet degradation of purified HA occurs only under acidic pH, consistent with previous reports on HYAL2 activity. 32,36 Although HYAL2 is known to be a cell surface protein, 37 we found little evidence of it on the surfaces of resting platelets. Instead, HYAL2 was detected exclusively on the surfaces of activated platelets.…”

Section: Discussioncontrasting

confidence: 71%

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

Albeiroti

Ayasoufi

Hill

et al. 2015

Blood

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• Platelet HYAL2 is stored in a-granules and upon activation it becomes surface expressed where it functions to degrade extracellular matrix.• Platelets from IBD patients contain lower HYAL2 protein and activity than those from non-IBD controls.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 a-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. (Blood. 2015; 125(9):1460-1469 Introduction Hyaluronan (HA) is a ubiquitous glycosaminoglycan and a major component of the extracellular matrix (ECM), and it has a crucial role in regulating inflammation.1 HA is produced by the HA synthase enzymes (HAS1-3) and is composed of repeating disaccharides of D-glucuronic acid and N-acetylglucosamine. Not only can HA be synthesized and released, but it can also form a voluminous pericellular coat that surrounds cells. The HA coat is either anchored to the cell surface through binding to specific cell-surface receptors, such as CD44, or it can be retained at the cell surface by sustained transmembrane interactions with its synthases.2 Interestingly, a growing body of literature suggests that different sizes of HA exert a wide spectrum of functions.3 Under normal conditions in tissues, HA is present in its high molecular weight (HMWHA) form (1 to 10 3 10 6 Da). HMWHA functions as a structural hydrating polymer and is also known to be antiinflammatory, 4 protecting from T-cellmediated liver injury and bleomycin-mediated lung injury in mice. 5,6 HMWHA also promotes the suppressive effects of regulatory CD4 1 CD251 T cells. 7Increased HA deposition has also been reported in many inflammatory diseases including inflammatory bowel disease (IBD), arthritis, and asthma. [8][9][10] Importantly, degradation of HA results in HA fragments that function as damage-associated molecular patterns. 11Fragmented HA contributes to wound healing, angiogenesis, and inflammation and is capable of signaling cellular responses through specific receptors. 12 For example, HA ...

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Section: Discussioncontrasting

confidence: 71%

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

Albeiroti

Ayasoufi

Hill

et al. 2015

Blood

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“…In this model, HYAL2 initiates HA degradation into small fragments that are endocytosed and degraded in lysosomes by HYAL1 and exoglycosidases (5,6). HYAL2 is a glycosylphosphatidylinositol-anchored protein (2) that could act at low pH at the cell surface (7). It has been suggested that HYAL2 resides in lysosomes in some cell types (8).…”

mentioning

confidence: 99%

“…Hyaluronidase 2 is a glycophosphatidylinositol-linked protein and a member of the hyaluronoglucosaminidase family (1,2). It is proposed to initiate the degradation of hyaluronan (HA), 3 an abundant glycosaminoglycan (GAG) in the extracellular matrix (ECM) of many vertebrate tissues (including heart valves), vitreous of the eye, and synovial fluid.…”

mentioning

confidence: 99%

Murine Hyaluronidase 2 Deficiency Results in Extracellular Hyaluronan Accumulation and Severe Cardiopulmonary Dysfunction

Chowdhury¹,

Hemming²,

Hombach‐Klonisch

et al. 2013

Journal of Biological Chemistry

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Background:The role of hyaluronidase 2 in hyaluronan degradation and cardiopulmonary function is largely uncharacterized. Results: Hyaluronidase 2-deficient mice accumulate extracellular hyaluronan, leading to defective cardiopulmonary function. Conclusion: Hyaluronidase 2 is essential for hyaluronan degradation and normal heart and lung health. Significance: Our studies suggest that hyaluronidase 2 deficiency should be considered as a contributor to cardiac pathologies in humans.

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“…HA metabolism is regulated by hyal enzymes in tissues and skin. HA HMW is digested into HA LMW by hyal-2, which is GPIanchored to the cell membrane (30). Subsequently, HA is endocytosed and intracellular processed by hyal-1 (31, 32).…”

Section: Hyal-2 Regulates Lc-dc Interactionsmentioning

confidence: 99%

Langerhans Cell–Dendritic Cell Cross-Talk via Langerin and Hyaluronic Acid Mediates Antigen Transfer and Cross-Presentation of HIV-1

Berg

Cardinaud

Aar

et al. 2015

The Journal of Immunology

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Human epidermal and mucosal Langerhans cells (LCs) express the C-type lectin receptor langerin that functions as a pattern recognition receptor. LCs are among the first immune cells to interact with HIV-1 during sexual transmission. In this study, we demonstrate that langerin not only functions as a pattern recognition receptor but also as an adhesion receptor mediating clustering between LCs and dendritic cells (DCs). Langerin recognized hyaluronic acid on DCs and removal of these carbohydrate structures partially abrogated LC–DC clustering. Because LCs did not cross-present HIV-1–derived Ags to CD8+ T cells in a cross-presentation model, we investigated whether LCs were able to transfer Ags to DCs. LC–DC clustering led to maturation of DCs and facilitated Ag transfer of HIV-1 to DCs, which subsequently induced activation of CD8+ cells. The rapid transfer of Ags to DCs, in contrast to productive infection of LCs, suggests that this might be an important mechanism for induction of anti–HIV-1 CD8+ T cells. Induction of the enzyme hyaluronidase-2 by DC maturation allowed degradation of hyaluronic acid and abrogated LC–DC interactions. Thus, we have identified an important function of langerin in mediating LC–DC clustering, which allows Ag transfer to induce CTL responses to HIV-1. Furthermore, we showed this interaction is mediated by hyaluronidase-2 upregulation after DC maturation. These data underscore the importance of LCs and DCs in orchestrating adaptive immunity to HIV-1. Novel strategies might be developed to harness this mechanism for vaccination.

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Hyal2 is a glycosylphosphatidylinositol-anchored, lipid raft-associated hyaluronidase

Cited by 51 publications

References 26 publications

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

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

Murine Hyaluronidase 2 Deficiency Results in Extracellular Hyaluronan Accumulation and Severe Cardiopulmonary Dysfunction

Langerhans Cell–Dendritic Cell Cross-Talk via Langerin and Hyaluronic Acid Mediates Antigen Transfer and Cross-Presentation of HIV-1

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