Abstract
Hyaluronan (HA) occurs in the body as a large, hydrating, space-filling, carbohydrate polymer in the extracellular matrix; it has both anti-angiogenic and immunosuppressive properties. Cleavage of HA results in the generation of variably sized fragments that stimulate multiple angiogenic and inflammatory responses in a size-specific manner. In this study, we report that platelets, as well as their megakaryocyte precursors, are unusual among somatic cells in that they contain only hyaluronidase 2 (HYAL2) but not HYAL1. Platelet HYAL2 is sufficient to cleave HA into fragments that are specific for inflammatory and angiogenic signaling; this process occurs in the absence of HYAL1, which is necessary in all other tissues to perform further HA degradation. Platelets can bind to HA, some of which derives from the stressed microvessel endothelial cell surface. Platelet-derived HYAL2 cleaves HA into fragments that stimulate mononuclear leukocytes in the immediate microenvironment to produce proinflammatory cytokines, including interleukin-6 and interleukin-8. Platelets, thus, are not only involved in hemostasis, the earliest step in wound healing, but are also important in the signaling of subsequent inflammatory and angiogenic steps. We hypothesize that aberrations in these sequential steps can promote chronic inflammation, as found in inflammatory bowel disease. The platelet may thus provide an interface between acute and chronic inflammation, wound healing, and their subsequent fibrotic responses.
| Original language | English |
|---|---|
| Pages (from-to) | 2254-2264 |
| Number of pages | 11 |
| Journal | American Journal of Pathology |
| Volume | 174 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2009 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Platelet-derived hyaluronidase 2 cleaves hyaluronan into fragments that trigger monocyte-mediated production of proinflammatory cytokines. / De La Motte, Carol; Nigro, Julie; Vasanji, Amit; Rho, Hyunjin; Kessler, Sean; Bandyopadhyay, Sudip; Danese, Silvio; Fiocchi, Claudio; Stern, Robert.
In: American Journal of Pathology, Vol. 174, No. 6, 06.2009, p. 2254-2264.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Platelet-derived hyaluronidase 2 cleaves hyaluronan into fragments that trigger monocyte-mediated production of proinflammatory cytokines
AU - De La Motte, Carol
AU - Nigro, Julie
AU - Vasanji, Amit
AU - Rho, Hyunjin
AU - Kessler, Sean
AU - Bandyopadhyay, Sudip
AU - Danese, Silvio
AU - Fiocchi, Claudio
AU - Stern, Robert
PY - 2009/6
Y1 - 2009/6
N2 - Hyaluronan (HA) occurs in the body as a large, hydrating, space-filling, carbohydrate polymer in the extracellular matrix; it has both anti-angiogenic and immunosuppressive properties. Cleavage of HA results in the generation of variably sized fragments that stimulate multiple angiogenic and inflammatory responses in a size-specific manner. In this study, we report that platelets, as well as their megakaryocyte precursors, are unusual among somatic cells in that they contain only hyaluronidase 2 (HYAL2) but not HYAL1. Platelet HYAL2 is sufficient to cleave HA into fragments that are specific for inflammatory and angiogenic signaling; this process occurs in the absence of HYAL1, which is necessary in all other tissues to perform further HA degradation. Platelets can bind to HA, some of which derives from the stressed microvessel endothelial cell surface. Platelet-derived HYAL2 cleaves HA into fragments that stimulate mononuclear leukocytes in the immediate microenvironment to produce proinflammatory cytokines, including interleukin-6 and interleukin-8. Platelets, thus, are not only involved in hemostasis, the earliest step in wound healing, but are also important in the signaling of subsequent inflammatory and angiogenic steps. We hypothesize that aberrations in these sequential steps can promote chronic inflammation, as found in inflammatory bowel disease. The platelet may thus provide an interface between acute and chronic inflammation, wound healing, and their subsequent fibrotic responses.
AB - Hyaluronan (HA) occurs in the body as a large, hydrating, space-filling, carbohydrate polymer in the extracellular matrix; it has both anti-angiogenic and immunosuppressive properties. Cleavage of HA results in the generation of variably sized fragments that stimulate multiple angiogenic and inflammatory responses in a size-specific manner. In this study, we report that platelets, as well as their megakaryocyte precursors, are unusual among somatic cells in that they contain only hyaluronidase 2 (HYAL2) but not HYAL1. Platelet HYAL2 is sufficient to cleave HA into fragments that are specific for inflammatory and angiogenic signaling; this process occurs in the absence of HYAL1, which is necessary in all other tissues to perform further HA degradation. Platelets can bind to HA, some of which derives from the stressed microvessel endothelial cell surface. Platelet-derived HYAL2 cleaves HA into fragments that stimulate mononuclear leukocytes in the immediate microenvironment to produce proinflammatory cytokines, including interleukin-6 and interleukin-8. Platelets, thus, are not only involved in hemostasis, the earliest step in wound healing, but are also important in the signaling of subsequent inflammatory and angiogenic steps. We hypothesize that aberrations in these sequential steps can promote chronic inflammation, as found in inflammatory bowel disease. The platelet may thus provide an interface between acute and chronic inflammation, wound healing, and their subsequent fibrotic responses.
UR - http://www.scopus.com/inward/record.url?scp=67049114124&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67049114124&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2009.080831
DO - 10.2353/ajpath.2009.080831
M3 - Article
C2 - 19443707
AN - SCOPUS:67049114124
VL - 174
SP - 2254
EP - 2264
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 6
ER -