Endotoxemia shifts neutrophils with TIMP-free gelatinase B/ MMP-9 from bone marrow to periphery and induces systematic upregulation of TIMP-1.

Endotoxemia shifts neutrophils with TIMP-free gelatinase B/ MMP-9 from bone marrow to periphery and induces systematic upregulation of TIMP-1. Haematologica. 2017 Aug 03;: Authors: Vandooren J, Swinnen W, Ugarte-Berzal E, Boon L, Dorst D, Martens E, Opdenakker G Abstract Lipopolysaccharides or endotoxins elicit an excessive host inflammatory response and lead to life-threatening conditions such as endotoxemia and septic shock. Lipopolysaccharides trigger mobilization and stimulation of leukocytes and exaggerated production of pro-inflammatory molecules including cytokines and proteolytic enzymes. Matrix metalloproteinase-9 (MMP-9) or gelatinase B, a protease stored in the tertiary granules of polymorphonuclear leukocytes, has been implicated in such inflammatory reactions. Moreover, several studies even pinpointed MMP-9 as a potential target molecule to counter excessive inflammation in endotoxemia. Whereas the early effect of lipopolysaccharides-induced inflammation in vivo on the expression of MMP-9 in various peripheral organs has been described, the effects on the bone marrow and during late stage endotoxemia remain elusive. We demonstrate that TIMP-free MMP-9 is a major factor in bone marrow physiology and pathology. By using a mouse model for late-stage endotoxemia, we show that lipopolysaccharides elicited a depletion of neutrophil MMP-9 in the bone marrow and a shift of MMP-9 and MMP-9-containing cells towards peripheral orga...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research