Gelatinase B deficiency protects against endotoxin shock.

Gelatinase B or matrix metalloproteinase-9 (MMP-9) is stored in the tertiary granules of polymorphonuclear leukocytes. These cells are key effectors in acute inflammatory diseases such as sepsis. Endotoxin leads to rapid release of gelatinase B from these granules in vitro and in vivo, but the role of this enzyme in bacterial sepsis and endotoxin shock remains unclear. We studied the clinical course of endotoxinemia and its relation with the expression of gelatinase B from the pool of circulating leukocytes in adult as well as in young mice in a model of endotoxin-induced shock and compared wild-type with gelatinase B-deficient mice. The gelatinase B-deficient mice were resistant to endotoxin shock, which implies that specific MMP-9 inhibition constitutes anapproach for the treatment of septic shock syndromes.