2019
DOI: 10.1182/blood.2018893594
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Platelet hyaluronidase-2 regulates the early stages of inflammatory disease in colitis

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 t… Show more

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Cited by 18 publications
(15 citation statements)
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“…While platelets do not bind to HA on the surface of ECs under normal conditions, platelets interact with HA produced by the inflamed vasculature during disease. 78 Once bound, platelets translocate hyaluronidase-2 (HYAL2) from within alpha-granules to the platelet surface, and subsequently degrade HA polymers from the cell surface. 79,80 HA fragments generated by HYAL2 can stimulate activation of monocytes, macrophages, and ECs presumably through toll-like receptors (TLR) 2 and 4.…”
Section: Ha As a Novel Immune Cell Recruitment Moleculementioning
confidence: 99%
See 1 more Smart Citation
“…While platelets do not bind to HA on the surface of ECs under normal conditions, platelets interact with HA produced by the inflamed vasculature during disease. 78 Once bound, platelets translocate hyaluronidase-2 (HYAL2) from within alpha-granules to the platelet surface, and subsequently degrade HA polymers from the cell surface. 79,80 HA fragments generated by HYAL2 can stimulate activation of monocytes, macrophages, and ECs presumably through toll-like receptors (TLR) 2 and 4.…”
Section: Ha As a Novel Immune Cell Recruitment Moleculementioning
confidence: 99%
“…36,81 This initiates activation of these cells, as well as the release of pro-inflammatory cytokines including IL-12, IL-1b, and TNF-a. 80 Degradation of HA by platelets has been demonstrated to regulate leukocyte transmigration, 78 and may function to control leukocyte recruitment to sites of inflammation in various disease states. In the case of lung inflammation, both TLRs 2 and 4 play crucial roles in the inflammatory response to HA fragments, but the specific contributions of platelets and ECs in this process is not well studied.…”
Section: Ha As a Novel Immune Cell Recruitment Moleculementioning
confidence: 99%
“…The inflammation caused by overactivated platelets can further promote the development of thrombosis, atherosclerosis, and cardiovascular diseases ( Barrett et al, 2019 ; Garshick et al, 2020 ; Schnorbus et al, 2020 ). Platelets exert critical roles in the development of inflammatory diseases such as inflammatory bowel disease (IBD) ( Chimen et al, 2019 ; Petrey et al, 2019 ; Nicolai and Massberg, 2020 ). Some studies have uncovered that platelets have important roles in the development of rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) ( Andrianova et al, 2019 ; Olumuyiwa-Akeredolu et al, 2019 ; Tessandier et al, 2020 ).…”
Section: Introductionmentioning
confidence: 99%
“…Additionally, this can aid in counseling and communicating risks to patients prior to undergoing pancreaticoduodenectomy or Whipple procedure. Another non-oncological GI disease process, inflammatory bowel disease (IBD), is associated with a reduction in HYAL2 in patients’ platelets, which has been shown to regulate trans-endothelial mononuclear cell migration in colonic tissue of IBD patients [ 61 ]. Patients who are suffering from Crohn’s disease, a type of inflammatory bowel disease, showed increased colonic fibroblast-specific KIAA1199, which is possibly induced by key inflammatory cytokine IL-6 [ 62 ].…”
Section: Hyaluronidases In Human Organs and Cancermentioning
confidence: 99%