ROLE OF MELANOMA GROWTH-STIMULATORY ACTIVITY (MGSA GRO) ON KERATINOCYTE FUNCTION IN WOUND HEARING/

Melanoma growth stimulatory activity/gro alpha (MGSA), a member of the alpha-chemokine family, is produced by a variety of dermal and epider mal cells and can act in a paracrine and autocrine fashion. However, l ittle is known about the importance of MGSA in wound healing. In this study, we quantified the levels of MGSA protein in burn blister and do nor site wound fluids. We studied the effects of MGSA on proliferation and migration of primary human keratinocytes and modulation of their integrin expression. Blister fluids contained 0.79 ng/ml (range 0.018 to 4.86 ng/ml) MGSA. Substantial increasing amounts of MGSA were found in donor site fluids from day 1 through day 5 with mean levels rangin g from 1.77 to 103 ng/ml at postoperative day 5, which correlated with increasing amounts of tumor necrosis factor alpha (r = 0.86), a known stimulus for MGSA production. In vitro proliferation experiments reve aled a maximum stimulation (2.6-fold) with 10 ng/ml MGSA for 7 days ov er unstimulated keratinocyte controls; the ED(50) was 0.2 ng/ml. DNA c ontent analysis revealed an increase in S phase with 10 ng/ml MGSA sti mulation. In cultured keratinocytes, MGSA enhanced the mean fluorescen ce intensity for alpha 6, while no significant change was seen for bet a 1, alpha 2 and alpha 5. We also studied the effect of topically appl ied MGSA (50 ng/cm(2)) on the healing of meshed split-thickness human skin grafts on athymic mice. In these wounds, MGSA stimulated the rate of epithelialization (P < 0.05) at day 7, and an increased proportion of mitotic keratinocytes was observed. Wound contraction was signific antly (P < 0.05) reduced on days 7 and 14 in the MGSA-treated group. T hese results suggest that MGSA participates in wound healing by stimul ating keratinocyte proliferation.