EFFECT OF MACROPHAGE STIMULATION ON COLLAGEN BIOSYNTHESIS IN THE HEALING WOUND

Immunomodulators that enhance macrophage function have been shown to b e beneficial in a number of wound-healing models in humans and in expe rimental animals. The exact mechanism of this improved healing is uncl ear. To assess the role of collagen biosynthesis, the immunomodulator glucan phosphate was utilized in two murine models of wound healing, i .e., colon anastomosis and full-thickness skin incision. Tensile stren gth was evaluated using computer-assisted constant velocity tensiometr y. Collagen biosynthesis was determined by assaying hydroxyproline con tent of wound hydrolysates by N-(9-fluorenyl)methoxycarbonyl/o-phthala ldehyde high-performance liquid chromatography. Experimental animals w ere treated with (1-3)-beta-D-glucan phosphate (250 mg/kg) intravenous ly 24 hours prior to colon anastomosis or skin incision. A second dose of glucan phosphate was given immediately postoperatively. Control an imals received dextrose and water (5% w/v) intravenously. Tensile stre ngth and hydroxyproline content were measured on postoperative Day 3. In the skin wound model, glucan phosphate treatment increased (P < 0.0 5) tensile strength by 42 per cent (342.5 +/- 12.2 vs 241.8 +/- 4.8 g) , and hydroxyproline content was increased by 23.5 per cent (242.0 +/- 14.4 vs 196.8 +/- 10.5 pmol/mu g; P < 0.05). In the glucan phosphate group, colon tensile strength was significantly (P < 0.05) increased b y 34 per cent (34.2 +/- 2.3 g vs 45.8 +/- 2.1 g), and hydroxyproline ! content was increased by 7 per cent (47.45 +/- 3.31 vs 44.34 +/- 3.74 pmol/mu g). These data indicate that macrophage modulation with gluca n phosphate will increase tensile strength in experimental colon and s kin wounds. In addition, we observed a positive correlation between gl ucan phosphate treatment, wound tensile strength, and collagen biosynt hesis.