Platelet hyaluronidase-2 regulates the early stages of inflammatory disease in colitis
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| Title: | Platelet hyaluronidase-2 regulates the early stages of inflammatory disease in colitis |
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| Authors: | Aaron C. Petrey, Dana R. Obery, Sean P. Kessler, Ash Zawerton, Bruno Flamion, Carol A. de la Motte |
| Source: | Petrey, A C, Obery, D R, Kessler, S P, Zawerton, A, Flamion, B & de la Motte, C A 2019, 'Platelet hyaluronidase-2 regulates the early stages of inflammatory disease in colitis', Blood, vol. 134, no. 9, pp. 765-775. https://doi.org/10.1182/blood.2018893594 |
| Publisher Information: | American Society of Hematology, 2019. |
| Publication Year: | 2019 |
| Subject Terms: | Blood Platelets, 0301 basic medicine, Inflammatory Bowel Diseases/immunology, Cells, Knockout, Hyaluronoglucosaminidase, GPI-Linked Proteins, Mice, 03 medical and health sciences, GPI-Linked Proteins/immunology, Animals, Humans, Colitis/immunology, Hyaluronic Acid/immunology, Hyaluronic Acid, Blood Platelets/immunology, Cells, Cultured, Inflammation, Mice, Knockout, 0303 health sciences, Cultured, Hyaluronoglucosaminidase/immunology, Endothelial Cells/immunology, Endothelial Cells, Inflammation/immunology, Colitis, Inflammatory Bowel Diseases, 3. Good health |
| Description: | Platelets are specialized cells essential for hemostasis that also function as crucial effectors capable of mediating inflammatory and immune responses. These sentinels continually survey their environment and discriminate between homeostatic and danger signals such as modified components of the extracellular matrix. The glycosaminoglycan hyaluronan (HA) is a major extracellular matrix component that coats the vascular lumen and, under normal conditions, restricts access of inflammatory cells. In response to tissue damage, the endothelial HA matrix enhances leukocyte recruitment and regulates the early stages of the inflammatory response. We have shown that platelets can degrade HA from the surface of activated endothelial cells via the enzyme hyaluronidase-2 (HYAL2) and that HYAL2 is deficient in platelets isolated from patients with inflammatory bowel disease (IBD). Platelets are known to be involved in the pathogenesis of several chronic disease states, including IBD, but they have been largely overlooked in the context of intestinal inflammation. We therefore wanted to define the mechanism by which platelet HYAL2 regulates the inflammatory response during colitis. In this study, we provide evidence that HA catabolism is disrupted in human intestinal microvascular endothelial cells isolated from patients with IBD. Furthermore, mice deficient in HYAL2 are more susceptible to an acute model of colitis, and this increased susceptibility is abrogated by transfusion of HYAL2-competent platelets. Finally, we show that platelets, via HYAL2-dependent degradation of endothelial HA, regulate the early stages of inflammation in colitis by limiting leukocyte extravasation. |
| Document Type: | Article |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.2018893594 |
| Access URL: | https://ashpublications.org/blood/article-pdf/134/9/765/1554331/blood893594.pdf https://pubmed.ncbi.nlm.nih.gov/31262781 https://researchportal.unamur.be/en/publications/95a2f13d-64a5-4058-9d3f-ffcc111f9575 https://doi.org/10.1182/blood.2018893594 https://pubmed.ncbi.nlm.nih.gov/31262781/ https://ashpublications.org/blood/article/134/9/765/260778/Platelet-hyaluronidase-2-regulates-the-early https://europepmc.org/article/MED/31262781 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716076 https://www.ncbi.nlm.nih.gov/pubmed/31262781 https://www.sciencedirect.com/science/article/pii/S000649712072327X https://pure.unamur.be/ws/files/54064036/blood893594.pdf |
| Accession Number: | edsair.doi.dedup.....1dce46e21463339be151de85c7843f5b |
| Database: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | Platelets are specialized cells essential for hemostasis that also function as crucial effectors capable of mediating inflammatory and immune responses. These sentinels continually survey their environment and discriminate between homeostatic and danger signals such as modified components of the extracellular matrix. The glycosaminoglycan hyaluronan (HA) is a major extracellular matrix component that coats the vascular lumen and, under normal conditions, restricts access of inflammatory cells. In response to tissue damage, the endothelial HA matrix enhances leukocyte recruitment and regulates the early stages of the inflammatory response. We have shown that platelets can degrade HA from the surface of activated endothelial cells via the enzyme hyaluronidase-2 (HYAL2) and that HYAL2 is deficient in platelets isolated from patients with inflammatory bowel disease (IBD). Platelets are known to be involved in the pathogenesis of several chronic disease states, including IBD, but they have been largely overlooked in the context of intestinal inflammation. We therefore wanted to define the mechanism by which platelet HYAL2 regulates the inflammatory response during colitis. In this study, we provide evidence that HA catabolism is disrupted in human intestinal microvascular endothelial cells isolated from patients with IBD. Furthermore, mice deficient in HYAL2 are more susceptible to an acute model of colitis, and this increased susceptibility is abrogated by transfusion of HYAL2-competent platelets. Finally, we show that platelets, via HYAL2-dependent degradation of endothelial HA, regulate the early stages of inflammation in colitis by limiting leukocyte extravasation. |
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| ISSN: | 15280020 00064971 |
| DOI: | 10.1182/blood.2018893594 |