DIFFERENCES IN CELLULAR INFILTRATE AND EXTRACELLULAR-MATRIX OF CHRONIC DIABETIC AND VENOUS ULCERS VERSUS ACUTE WOUNDS

In diabetic patients, wound healing is impaired. We studied the pathog enesis behind this clinical observation by characterizing the pattern of deposition of extracellular matrix (ECM) molecules and the cellular infiltrate in chronic (>8 wk) diabetic wounds, compared with chronic venous ulcers and an acute wound healing model. Punch biopsies were ob tained from the chronic ulcer margins and control samples were collect ed from upper leg skin 5, 19, 28 d and 12 and 18 mo postwounding (p.w. ), T cells, B cells, plasma cells, granulocytes and macrophages, and t he ECM molecules fibronectin (FN), chondroitin sulfate (CS), and tenas cin (TN) were visualized using immunohistochemical techniques. Express ion of FN, CS, and TN was detected in dermal tissue early in normal wo und healing (5-19 d p.w.). Abundant staining was seen 3 mo p.w., retur ning to prewounding levels after 12-18 mo p.w. In the dermis of chroni c diabetic and venous ulcers with a duration of 12 mo or more, a prolo nged presence of these ECM molecules was noted. Compared with normal w ound healing: (i) the CD4/CD8 ratio in chronic wounds was significantl y lower (p < 0.0027) due to a relatively lower number of CD4(+) T cell s; (ii) a significantly higher number of macrophages was present in th e edge of both type of chronic ulcers (p < 0.001 versus day 29 p.w.); and (iii) more B cells and plasma cells were detected in both type of chronic wounds compared with any day in the acute wound healing model (p < 0.04 for CD20(+) and p < 0.01 for CD79a(+) cells). These data ind icate that important differences exist in the cellular infiltrate and ECM expression patterns of acute, healing versus chronic wounds, which may be related to the nonhealing status of chronic wounds.