alpha 1-Antichymotrypsin activity correlates with and may modulate matrix metalloproteinase-9 in human acute wounds

作者:Reiss Matthew J; Han Yuan Ping; Garner Warren L*
来源:Wound Repair and Regeneration, 2009, 17(3): 418-426.
DOI:10.1111/j.1524-475X.2009.00476.x

摘要

Matrix metalloproteinase-9 (MMP-9) plays a central role in many physiologic processes including acute and the chronic wounds. MMP-9 is not routinely expressed in healthy tissues but is promptly expressed as a proenzyme and converted into active enzyme after tissue injury. The mechanisms involved, including the activators and inhibitors for this enzyme in human tissue remain largely obscure. We recently identified alpha 1-antichymotrypsin (alpha 1-ACT), an acute phase factor, as a potent inhibitor controlling activation of pro-MMP-9 by human skin. The aim of this study is to establish the clinical relevance of the inhibitor in cutaneous wound healing. Fluids from acute burn blisters and conditioned media from skin explants of burn patients were analyzed. We observed that the presence pro-MMP-9 and its activation correlated with the proximity to and degree of injury. Early after trauma, massive levels of wound alpha 1-ACT were associated with an absence of pro-MMP-9 activation. Conversely, the active MMP-9 occurs simultaneously with inactivation of alpha 1-ACT. Our results suggest a role for alpha 1-ACT as a physiologic inhibitor of MMP-9 activation in human wound healing.

  • 出版日期2009-6