Adenosine Triphosphate Hydrolysis Reduces Neutrophil Infiltration and Necrosis in Partial-Thickness Scald Burns in Mice

Bayliss, Jill MS*; DeLaRosa, Sara BS; Wu, Jianfeng PhD; Peterson, Jonathan R. BA; Eboda, Oluwatobi N. BS; Su, Grace L. MD*‡; Hemmila, Mark MD; Krebsbach, Paul H. DDS, PhD; Cederna, Paul S. MD; Wang, Stewart C. MD, PhD; Xi, Chuanwu PhD§; Levi, Benjamin MD

doi: 10.1097/BCR.0b013e31829b36d6
Original Articles: 2013 ABA Papers

Extracellular adenosine triphosphate (ATP), present in thermally injured tissue, modulates the inflammatory response and causes significant tissue damage. The authors 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% TBSA partial-thickness scald burn by dorsal skin immersion in a water bath at 60 or 20°C (nonburn 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, elastase, and Ki-67 staining. Tumor necrosis factor (TNF)-α and interferon (IFN)-β expression were measured through quantitative real-time polymerase chain reaction. At 24 hours, the amount of neutrophil infiltration was different between the burn and burn + apyrase groups (P < .001). Necrosis was less extensive in the apyrase group when compared with 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 < .05). However, Ki-67 signaling was not significantly different among the groups. The results of this study support the role of extracellular ATP in neutrophil activity. The authors 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 because of TNF-α and IFN-β signaling. Apyrase could be used as topical inflammatory regulators to quell the injury caused by inflammation.

From the Departments of *Medicine and Surgery, University of Michigan Medical School, Ann Arbor; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor; §Veterans Administration Ann Arbor Healthcare Systems, Michigan; and Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor.

The research is partially supported by the National Institutes of Health grant (R01GM098350-02) to C. Xi and S.C. Wang. The other authors declare no conflict of interest.

J. Bayliss and S. DeLaRosa share equal authorship.

Sara DeLaRosa is a Howard Hughes Medical Institute Medical Research Fellow.

Address correspondence to Benjamin Levi, MD, Department of Surgery, University of Michigan Medical School, 1500 East Medical Center Drive, Taubman Center, SPC 5340, Ann Arbor, Michigan 48109-0219.

© 2014 The American Burn Association