Inactive matrix metalloproteinase 2 is a normal constituent of human glomerular basement membrane. An immune-electron microscopic study

Remodelling of the extracellular matrix requires tight control not only of matrix synthesis, but also of matrix degradation. Control of matrix degrada tion is achieved mainly through the matrix metalloproteinase (MMP) enzymes. In the glomerulus, MMP-2 and MMP-9 are believed to be particularly importa nt, as they have activity against type IV collagen. This study has demonstr ated by immune-electron microscopy that most of the immunoreactivity for MM P-2 in the normal glomerulus is located within the glomerular basement memb ranes and mesangial matrix. mRNA for MMP-2 is also detectable in normal glo meruli, but the other main gelatinase, MMP-9, could not be localized by imm une-electron microscopy. In the normal glomerulus, it seemed likely that MM P-2 is present in an inactive form. To confirm this, in situ zymography was carried out using frozen sections of normal kidney. Baseline activity of n ormal kidney was relatively weak, but this was dramatically increased by ch emical activation of metalloproteinases, The results imply that MMP-2, in a n inactive form, is a normal constituent of the extracellular matrix and gl omerular basement membranes. Activation would presumably render the matrix 'self-degrading'; membrane-bound MMPs (MT-MMPs) seem particularly likely to be involved in leukocyte penetration of basement membranes in inflammation . Copyright (C) 2000 John Wiley & Sons, Ltd.