Platelet-Derived Hyaluronidase 2 Cleaves Hyaluronan into Fragments that Trigger Monocyte-Mediated Production of Proinflammatory Cytokines
Platelet-Derived Hyaluronidase 2 Cleaves Hyaluronan into Fragments that Trigger Monocyte-Mediated Production of Proinflammatory Cytokines
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DOI：
10.2353/ajpath.2009.080831
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发表时间：
2009-06-01
影响因子：
6
通讯作者：
Stern, Robert
中科院分区：
文献类型：
--
作者：
de la Motte, Carol;Nigro, Julie;Stern, Robert
Hybryonan（RA）在体内作为细胞外基质中的大的、水合的、空间填充的碳水化合物聚合物发生;它具有抗血管生成和免疫抑制特性。HA的裂解导致产生尺寸特异性的片段，其以尺寸特异性的方式刺激多种血管生成和炎症反应。在这项研究中，我们报道了血小板以及它们的巨核细胞前体细胞在体细胞中是不寻常的，因为它们只含有透明质酸酶2（HYAL 2）而不含HYAL 1。血小板HYAL 2足以将HA切割成对炎症和血管生成信号特异性的片段;该过程在缺乏HYAL 1的情况下发生，HYAL 1在所有其他组织中是进行进一步HA降解所必需的。血小板可以与RA结合，其中一些来自应激的微血管内皮细胞表面。血小板衍生的HYAL 2将RA切割成片段，这些片段刺激直接微环境中的单核白细胞产生促炎细胞因子，包括白细胞介素-6和白细胞介素-8。因此，血小板不仅参与止血，伤口愈合的最早步骤，而且在随后的炎症和血管生成步骤的信号传导中也很重要。我们假设这些顺序步骤中的异常可以促进慢性炎症，如在炎症性肠病中发现的。因此，血小板可以在急性和慢性炎症、伤口愈合及其随后的纤维化反应之间提供界面。(Am J Pathol 2009，174：2254-2264; DOI：10.2353/ajpath.2009.080831）
Hyaluronan (RA) 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 RA, some of which derives from the stressed microvessel endothelial cell surface. Platelet-derived HYAL2 cleaves RA 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. (Am J Pathol 2009, 174:2254-2264; DOI: 10.2353/ajpath.2009.080831)