Editors' ChoiceTransplant

Sounding the Alarm for RAGE

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Sci. Signal.  09 Sep 2014:
Vol. 7, Issue 342, pp. ec249
DOI: 10.1126/scisignal.2005875

Only 20% of lungs are transplantable because traumatic brain injury, a major cause of death in organ doors, may induce acute lung injury. High-mobility group box-1 (HMGB1) release from the injured brain likely contributes to acute lung injury in donors by preferentially interacting with receptor for advanced glycation end products (RAGE) in the lung (see Nicolls and Laubach). Weber et al. found that blocking the HMGB1-RAGE axis improves lung function in murine donors with traumatic brain injury and after transplant. In translational studies, lungs sourced from donors with high HMGB1 levels had worse pulmonary function after transplant. Targeting the HMGB1-RAGE axis may increase the number of lungs available for transplantation and improve patient outcomes.

D. J. Weber, A. S. A. Gracon, M. S. Ripsch, A. J. Fisher, B. M. Cheon, P. H. Pandya, R. Vittal, M. L. Capitano, Y. Kim, Y. M. Allette, A. A. Riley, B. P. McCarthy, P. R. Territo, G. D. Hutchins, H. E. Broxmeyer, G. E. Sandusky, F. A. White, D. S. Wilkes, The HMGB1-RAGE axis mediates traumatic brain injury–induced pulmonary dysfunction in lung transplantation. Sci. Transl. Med. 6, 252ra124 (2014). [Abstract]

M. R. Nicolls, V. E. Laubach, Traumatic brain injury: Lungs in a RAGE. Sci. Transl. Med. 6, 252fs34 (2014). [Abstract]