Proteinases, their inhibitors, and cytokine profiles in acute wound fluid

Wound healing is a complex process involving the interactions of many diffe rent cell types, matrix components and biological factors, including protei nases and cytokines. This study compared the levels of proteinases (matrix metalloproteinases and plasminogen activators), proteinase inhibitors (tiss ue inhibitors of metalloproteinases and plasminogen activator inhibitors), inflammatory cytokines and growth factors in acute wound fluid samples coll ected from the surgical drains of elective breast (n = 24) and colorectal ( n = 26) patients on the first postoperative day. Gelatin zymography was use d to determine matrix metalloproteinase-2 and -9 levels, quenched fluoresce nce substrate hydrolysis was applied for total MMP activity and enzyme-link ed immunoassays were used to quantitate other factors. Colorectal wound flu id samples showed significantly (p < 0.05) greater levels of the matrix met alloproteinases (MMP-1,2, 3, and 9), tissue inhibitor of metalloproteinases -1, urokinase plasminogen activator receptor and the inflammatory cytokines (interleukin-1<beta>, -6, and tumor necrosis factor-alpha); e.g., matrix m etalloproteinase-3 colon; median 275 (range 11-2.530) ng/ml: breast: 530-40 0. However, tissue plasminogen activator and growth factor levels (epiderma l growth factor, platelet-derived growth factor, basic fibroblast growth fa ctor, transforming growth factor-beta1) were significantly greater in breas t samples: e.g., epidermal growth factor breast 468 (103-1,444) pg/ml: colo n 57(1-573). There was no difference in the levels of urokinase type plasmi nogen activator, plasminogen activator inhibitor-1 and -2, tissue inhibitor of metalloproteinases -2 or vascular endothelial growth factor. Acute woun d fluid from different surgical wounds showed different profiles of protein ases, proteinase inhibitors, and cytokines. This may lead to differences in the rate of tissue remodeling and therefore healing in these two wounds in vivo.