Increased plasma levels of matrix metalloproteinase-9 are associated with the severity of chronic urticaria

Background Matrix metalloproteinase (MMP)-9 is produced by many inflammatory cells such as macrophages, neutrophils, mast cells, eosinophils and T lymphocytes. Activated T cells are capable, through cell-cell contact, of inducing MMP-9 expression in human mast cells. Objective To investigate the activation status of peripheral CD4(+) T cells and the level of MMP-9 in the plasma of patients with chronic urticaria (CU), and whether MMP-9 levels are in association with CU severity. Methods Study subjects included 29 patients with CU and 30 healthy control subjects. At the time of assessment, patients were divided into subgroups according to urticarial severity. Plasma levels of total MMP-9 (free pro-MMP-9 and free MMP-9) were determined by ELISA. CD4(+) lymphocytes were positively selected with magnetic microbeads. After 48 h of activation, CD4(+) T cells were assayed for both nuclear factor-kappaB (NF-kappaB) expression and proliferation. Results Plasma levels of MMP-9 were found to be significantly higher in 29 CU patients compared with 18 healthy controls (186+/-174 vs. 31+/-21 ng/mL, P<0.0001). We also found a significant correlation between MMP-9 levels and urticarial severity (r=0.92, P<0.001). In addition, CD4(+) T cells from CU patients expressed higher levels of NF-kappaB than CD4(+) T cells from healthy controls (82+/-30 vs. 69+/-20 optical density, P=0.007). Finally, as compared with seven healthy individuals, DNA synthesis in CD4(+) T cells from seven CU patients was found to be significantly elevated (1000+/-240 vs. 751+/-166 counts per minute, P=0.01). Conclusion Increased levels of MMP-9 are found in CU patients, and particularly among those with severe disease. We also demonstrated that CD4(+) T cells from such patients are highly activated.