Gelatinase B: a tuner and amplifier of immune functions

Gelatinase B (matrix metalloproteinase-9) is a secreted multidomain enzyme that is important for the remodeling of the extracellular matrix and the mi gration of normal and tumor cells. It cleaves denatured collagens (gelatins ) and type IV collagen, which is present in basement membranes. In the immu ne system, this cleavage helps lymphocytes and other leukocytes to enter an d leave the blood and lymph circulations. Gelatinase B also cleaves myelin basic protein and type II gelatins, and this clipping leads to remnant epit opes that generate autoimmunity, the so-called REGA model of autoimmunity. Recently, gelatinase B has been found to process cytokines and chemokines, resulting in skewed immune functions. Therefore, gelatinase B, often consid ered as a pure effector molecule, acts as a switch and catalyst in both inn ate and specific immunity, and constitutes a prototypic example of the regu lation of immune functions by proteolysis.