Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-α, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages

被引:68
作者
Dong, Yifei [1 ]
Arif, Arif [1 ]
Olsson, Mia [1 ,2 ]
Cali, Valbona [3 ]
Hardman, Blair [1 ]
Dosanjh, Manisha [1 ]
Lauer, Mark [3 ]
Midura, Ronald J. [3 ]
Hascall, Vincent C. [3 ]
Brown, Kelly L. [2 ]
Johnson, Pauline [1 ]
机构
[1] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada
[2] British Columbia Childrens Hosp, Res Inst, Dept Pediat, Vancouver, BC, Canada
[3] Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA
基金
加拿大自然科学与工程研究理事会; 瑞典研究理事会; 加拿大健康研究院;
关键词
WEIGHT HYALURONAN; AIRWAY HYPERRESPONSIVENESS; RECEPTOR CD44; KAPPA-B; ACID; EXPRESSION; BINDING; MODEL; OLIGOSACCHARIDES; DEPOSITION;
D O I
10.1038/srep36928
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 costimulatory 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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页数:15
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