APOPTOSIS MEDIATES THE DECREASE IN CELLULARITY DURING THE TRANSITION BETWEEN GRANULATION-TISSUE AND SCAR

Granulation tissue formation and contraction is an important step of s econd intention wound healing. Granulation tissue develops from the co nnective tissue surrounding the damaged or missing area and its cellul ar components are mainly small vessel and inflammatory cells as well a s fibroblasts and myofibroblasts. As the wound closes and evolves into a scar, there is an important decrease in cellularity; in particular myofibroblasts disappear. The question arises as to which process is r esponsible for this cellular loss. During a previous investigation on the expression of alpha-smooth muscle actin in myofibroblasts (Darby I , Skalli O, Gabbiani G, Lab Invest, 1990, 63:21-29), we have observed that in late phases of wound healing, many myofibroblasts show changes compatible with apoptosis and suggested that this type of cell death could be responsible for the disappearance of myofibroblasts. We have now tested this hypothesis by means of morphometry at the electron mic roscopic level and by in situ end labeling of fragmented DNA. Our resu lts indicate that the number of myofibroblastic and vascular cells und ergoing apoptosis increases as the wound closes and support the assump tion that this is the mechanism of granulation tissue evolution into a scar. The regulation of apoptotic phenomena during wound healing may be important in scar establishment and development of pathological sca rring.