Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-α, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages.
Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-α, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages.
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DOI：
10.1038/srep36928
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发表时间：
2016-11-21
影响因子：
4.6
通讯作者：
Johnson P
中科院分区：
文献类型：
--
作者：
Dong Y;Arif A;Olsson M;Cali V;Hardman B;Dosanjh M;Lauer M;Midura RJ;Hascall VC;Brown KL;Johnson P
细胞外基质糖胺聚糖，透明质酸，已被描述为组织炎症的调节剂，据报道透明质酸片段刺激先天性免疫细胞。高分子量的透明质酸通常存在于组织中，但在炎症时产生较低分子量的片段。目前尚不清楚这些透明质酸片段是否诱导炎症反应或炎症的结果。在这项研究中，小鼠骨髓来源的巨噬细胞和树突状细胞（DC）刺激不同大小的透明质酸从不同的来源，片段透明质酸，透明质酸酶和重链修饰的透明质酸（HA-HC）。测量关键促炎分子、肿瘤坏死因子α、白细胞介素-1 β、白细胞介素-12、CCL 3和共刺激分子CD 40和CD 86。只有人脐带透明质酸、牛睾丸和链霉菌透明质酸酶刺激巨噬细胞和DC，然而，发现这些试剂被内毒素污染，多粘菌素B处理不能完全去除内毒素。相反，药物级透明质酸和透明质酸片段不能刺激体外衍生或离体巨噬细胞和DC，并且在气管内滴注到小鼠肺中后不诱导白细胞募集。因此，在我们的炎症模型中，无内毒素的药用级透明质酸不刺激巨噬细胞和DC。这些结果强调了确保透明质酸制剂不含内毒素的重要性。
The extracellular matrix glycosaminoglycan, hyaluronan, has been described as a regulator of tissue inflammation, with hyaluronan fragments reported to stimulate innate immune cells. High molecular mass hyaluronan is normally present in tissues, but upon inflammation lower molecular mass fragments are generated. It is unclear if these hyaluronan fragments induce an inflammatory response or are a consequence of inflammation. In this study, mouse bone marrow derived macrophages and dendritic cells (DCs) were stimulated with various sizes of hyaluronan from different sources, fragmented hyaluronan, hyaluronidases and heavy chain modified-hyaluronan (HA-HC). Key pro-inflammatory molecules, tumour necrosis factor alpha, interleukin-1 beta, interleukin-12, CCL3, and the co-stimulatory molecules, CD40 and CD86 were measured. Only human umbilical cord hyaluronan, bovine testes and Streptomyces hyaluronlyticus hyaluronidase stimulated macrophages and DCs, however, these reagents were found to be contaminated with endotoxin, which was not fully removed by polymyxin B treatment. In contrast, pharmaceutical grade hyaluronan and hyaluronan fragments failed to stimulate in vitro-derived or ex vivo macrophages and DCs, and did not induce leukocyte recruitment after intratracheal instillation into mouse lungs. Hence, endotoxin-free pharmaceutical grade hyaluronan does not stimulate macrophages and DCs in our inflammatory models. These results emphasize the importance of ensuring hyaluronan preparations are endotoxin free.
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