Title:Targeting Matrix Metalloproteinases in Acute Inflammatory Shock Syndromes
VOLUME: 15 ISSUE: 7
Author(s):Zheng Qiu, Jialiang Hu, Philippe E. Van den Steen and Ghislain Opdenakker
Affiliation:Laboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
Keywords:Inflammation, lipopolysaccharide, matrix metalloproteinase, MMP inhibitor, neutrophil, sepsis, Acute Inflammatory Shock, gene knockout, extracellular matrix, intravascular milieu
Abstract:The integrity of the vascular wall and its intrinsic basement membrane structures ensure that plasma and the
corpuscular elements of the blood remain confined to the intravascular milieu and can enter into the extravascular
compartment in a well controlled fashion in cases of tissue infection or inflammation. However, sometimes inflammatory
stimuli act on blood leukocytes and on endothelial cells from within the blood vessels and in an overwhelming way,
leading to inflammatory shock syndromes. These severe conditions with high mortality rates are characterized by
intravascular neutrophil degranulation, permeability changes of endothelia and disintegration of basement membranes and
lead to almost uncontrollable edema, coagulation changes and multi-organ failure. Matrix metalloproteinases (MMPs)
have been functionally linked with septic and endotoxin shock, with cytokine release syndromes and with acute lung
injury (ALI) and acute respiratory distress syndrome (ARDS). Here we review a number of association studies, compare
inflammatory shock data from gene knockout studies in mice and provide some insights from recent investigations with
inhibitors of MMPs. This evaluation strengthens the expectation that MMP inhibitors, in particular those blocking
neutrophil proteases, may become useful in the early phase of acute inflammatory shock syndromes.
