Adenosine triphosphate hydrolysis reduces neutrophil infiltration and necrosis in partial-thickness scald burns in mice.
Adenosine triphosphate hydrolysis reduces neutrophil infiltration and necrosis in partial-thickness scald burns in mice.
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DOI：
10.1097/bcr.0b013e31829b36d6
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Levi B
中科院分区：
文献类型：
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作者：
Bayliss J;Delarosa S;Wu J;Peterson JR;Eboda ON;Su GL;Hemmila M;Krebsbach PH;Cederna PS;Wang SC;Xi C;Levi B
存在于热损伤组织中的细胞外ATP调节炎症反应并导致显著的组织损伤。我们假设，中性粒细胞浸润和随后的组织坏死将减轻在烧伤部位去除ATP依赖性信号。通过将背部皮肤浸入60°C或20°C的水浴中，使小鼠经受30%总体表面积的部分厚度烧伤（非烧伤对照）。在治疗组中，ATP水解酶，腺苷三磷酸双磷酸酶，在损伤后立即直接应用于该部位。在24小时和5天后收获皮肤用于苏木精和伊红染色（H&E）、弹性蛋白酶和Ki-67染色。通过qRT-PCR测量TNF-α和IFN-β表达。在24小时，烧伤组和烧伤+腺苷三磷酸双磷酸酶组之间的中性粒细胞浸润量不同（p<0.001）。24小时和5天时，与烧伤组相比，三磷酸腺苷双磷酸酶组的坏死范围较小。腺苷三磷酸双磷酸酶组24 h TNF-α和IFN-β表达低于烧伤组（p <0.05）。然而，Ki-67信号在各组之间没有显著差异。我们的研究结果支持细胞外ATP在中性粒细胞活性中的作用。我们证明，ATP水解在烧伤部位减轻中性粒细胞对热损伤的反应，并减少组织坏死。这种炎症和组织坏死的减少至少部分是由于TNF-α和IFN-β信号传导。三磷酸腺苷双磷酸酶可用作局部炎症调节剂，以平息炎症引起的损伤。
Extracellular ATP, present in thermally-injured tissue, modulates the inflammatory response and causes significant tissue damage. We hypothesize that neutrophil infiltration and ensuing tissue necrosis would be mitigated by removing ATP-dependent signaling at the burn site. Mice were subjected to 30% total-body- surface-area partial-thickness scald burn by dorsal skin immersion in a water bath at 60°C or 20°C (non-burn controls). In the treatment arm, an ATP hydrolyzing enzyme, apyrase, was applied directly to the site immediately after injury. Skin was harvested after 24 hours and 5 days for hematoxylin and eosin stain (H&E), elastase, and Ki-67 staining. TNF-α and IFN-β expression were measured through qRT-PCR. At 24 hours, the amount of neutrophil infiltration was different between the burn and burn + apyrase groups (p<0.001). Necrosis was less extensive in the apyrase group when compared to the burn group at 24 hours and 5 days. TNF-α and IFN-β expression at 24 hours in the apyrase group was lower than in the burn group (p <0.05). However, Ki-67 signaling was not significantly different among the groups. Our results support the role of extracellular ATP in neutrophil activity. We demonstrate that ATP hydrolysis at the burn site allays the neutrophil response to thermal injury and reduces tissue necrosis. This decrease in inflammation and tissue necrosis is at least partially due to TNF-α and IFN-β signaling. Apyrase could be used as topical inflammatory regulators to quell the injury caused by inflammation.