No abstract

Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti-inflammatory mediator. Using cultured human cells, we show here that APC up-regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization. In a full-thickness rat skin-healing model, a single topical application of APC enhanced wound healing compared to saline control. APC-treated wounds had markedly more blood vessels on day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The broad spectrum matrix metallo-proteinase, GM6001, prevented the ability of APC to promote wound healing. In summary, our results show that APC promotes cutaneous wound healing via a complex mechanism involving stimulation of angiogenesis and inhibition of inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds.

If neutrophils predominate, the wound is probably less than a couple of days old. When macrophages are abundant the wound is probably a few days to weeks old. However, as expected from the review of the literature, the inflammatory cell infiltrate may be low or absent in burn wounds, which can render determination of the age of burn wounds difficult.

Paraffin-embedded sections from a variety of epidermal lesions were stained with fluorescein isothiocyanate-labeled concanavalin A and examined by a fluorescence microscope. Seventy-six normal, hyperplastic, and neoplastic tissues were examined. Lectin binding was demonstrated in all malignant tumors, the fluorescence being confined to the plasma membrane of the tumor cells. Normal and hyperplastic tissues either failed to stain or showed a grossly diminished level of fluorescence. The distinction between malignant and normal of hyperplastic cells was clear-cut and definite.