Abstract
METHODS: Forty rabbits were used. One ear was rendered ischemic, and 4 wounds were created on each ear. Two were treated with ATP-vesicles and the other 2 were treated with Regranex or normal saline. Among the rabbits, 24 were used for healing comparison (15 saline, and 9 Regranex), and the others were sacrificed at different days for histologic and immunohistologic studies. RESULTS: ATP-vesicle treated wounds healed significantly faster (p<0.01) than the control wounds. Strikingly, granulation tissue started to appear within 24 hours postoperatively in ATP-vesicles-treated wounds while no such growth in wounds treated by Regranex or saline. ATP-vesicle treated wound tissue immunohistochemical analysis of CD61, CD34, Anti-MAC387, PCNA, Anti-Brdu, CD68, CD163, and IL-13R revealed massive macrophage accumulation in the wound wall and cavity with active proliferation along with enhanced collagen synthesis. The activation of IL-13R by ATP-vesicles shows direct collagen production by macrophages via an alternative pathway. Primary human monocyte/ macrophage culture confirmed their direct collagen production in the presence of ATP-vesicles. Collagen secretion was increased significantly (p<0.05) with dose and time of ATP- vesicle treatment.
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