Aberrant tubulointerstitial immunoexpression of matrix metalloproteinases MMP-2, MMP-9 and tissue inhibitor of matrix proteinase-2 (TIMP-2) in acute cellular rejection of human renal allograft.

Acute cellular rejection (ACR) may initiate chronic allograft dysfunction with alterations in the extracellular matrix compartment (ECM). Turnover of ECM proteins is regulated by matrix metalloproteinases (MMPs). The aim of the present study was to determine the immunoexpression of MMP-2, MMP-9 and TIMP-2 in ACR, and to examine the relationship between expression of MMPs and monocytes/macrophages, transforming growth factor beta-1 (TGFbeta-1), and alpha-smooth muscle actin (alpha-SMA). Immunoperoxidase study with antibodies against MMP-2, MMP-9, TIMP-2, CD68, TGFbeta-1 and alpha-SMA was carried out on 24 renal allograft biopsy specimens from patients with ACR and 11 allograft biopsy specimens from patients with no signs of rejection. Our study revealed increased immunoexpression of MMP-2, MMP-9 and TIM-2 in ACR as compared with controls, and significant positive correlations between immunostaining of MMP-2 and TGF-beta-1, as well as between MMP-2 and alpha-SMA. Increased immunoexpression of MMP-9 was positively correlated with alpha-SMA, and the number of interstitial CD68+cells. In conclusion our study supports a role of gelatinases in tissue damage in human renal acute cellular allograft rejection and provides some interesting insights into early renal remodeling which may lead to chronic allograft dysfunction.