Unknown

Dataset Information

0

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


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 lipopolysaccharide-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 organs, a pattern which was primarily associated with a relocation of CD11bhighGr-1high cells. In contrast, analysis of the tissue inhibitors of metalloproteinases was in line with a natural, systematic upregulation of TIMP-1, the main tissue inhibitor of TIMP-free MMP-9, and a general shift toward control of matrix metalloproteinase activity by tissue inhibitors of metalloproteinases.

SUBMITTER: Vandooren J 

PROVIDER: S-EPMC5622851 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

altmetric image

Publications

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

Vandooren Jennifer J   Swinnen Wannes W   Ugarte-Berzal Estefania E   Boon Lise L   Dorst Daphne D   Martens Erik E   Opdenakker Ghislain G  

Haematologica 20170803 10


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  ...[more]

Similar Datasets

| S-EPMC2154419 | biostudies-literature
| S-EPMC9178525 | biostudies-literature
| S-EPMC8158883 | biostudies-literature
| S-EPMC8579102 | biostudies-literature
| S-EPMC3157227 | biostudies-literature
| S-EPMC5107848 | biostudies-literature
| S-EPMC3980597 | biostudies-literature
| S-EPMC8469609 | biostudies-literature
| S-EPMC7101851 | biostudies-literature
| S-EPMC2676002 | biostudies-literature