Abstract 630: Broad-spectrum Inhibition of the CC-Chemokine Class Accelerates Wound Healing.
Introduction: Wound healing is a multistep process involving inflammation, proliferation and remodelling at the wound site. Macrophages are important in the inflammatory stage to remove debris, however excessive macrophage accumulation may prolong the inflammatory response leading to prolonged wound healing, excessive scar formation and loss of function at the injury site. In the wound healing process, the CC-chemokine class is involved in the recruitment of macrophages to the wound site. Inhibition of the CC-chemokine class to reduce macrophage infiltration may present as strategy to increase wound closure and reduce scar formation.
Aim: To determine if broad spectrum CC-chemokine inhibitor, 35K, can improve wound healing by reducing the inflammatory response and preventing scar formation.
Results: Two full-thickness wounds were created on the dorsum, one each side of the midline, of C57BL6 mice. Wounds were treated topically with PBS or 35K protein daily for 10 days. Wounds treated with 35K closed significantly faster than PBS treated wounds between days 4 - 6 (p<0.05) post-wounding. Laser Doppler measurements revealed 35K significantly increased blood flow at the early (day 3-4) and late stages (day 10) of wound repair. Ten days after wounding, collagen was significantly lower in the 35K treated wounds (25.3% p<0.05). There were also reductions in neovessels (CD31, 39%, p<0.001), arterioles (alpha actin, 48% p<0.01) and macrophages (CD68, 25%), as a percentage of wound area, in 35K treated wounds. In wound tissue collected on day 4 (early stage) post-wounding, 35K treatment had an inhibitory effect on CCL2 and CCL5 protein by 41% (p<0.05) and 36% (p<0.05) respectively, and were reduced by 22% and 66% (p<0.05) respectively at day 10 (late stage) wound healing. Consistent with this, mRNA levels of p65 also decreased in both day 4 (34%, p<0.05) and day 10 (62%, p<0.05) wounds treated with 35K.
Conclusion: The CC-chemokine class appears to play a key role in wound repair as topical application of CC-chemokine inhibitor 35K promoted wound healing. This was likely to be via inhibition of inflammation and promotion of blood flow recovery in the early stages of wound repair, thereby resulting in less scar formation.
Author Disclosures: A. Ridiandries: None. J.T.M. Tan: None. C.A. Bursill: None.
- © 2015 by American Heart Association, Inc.