Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0034063 (
pulmonary edema
)
10,665
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
ADAM15
is a disintegrin and metalloprotease recently implicated in cancer and chronic immune disorders. We have recently characterized
ADAM15
as a mediator of endothelial barrier dysfunction. Whether this molecule contributes to acute inflammation has not been evaluated. The purpose of this study was to investigate the role of
ADAM15
in mediating pulmonary microvascular leakage during acute inflammatory injury. Immunofluorescent staining and Western blotting revealed that the endothelium was the main source of
ADAM15
in lung tissue. In a mouse model of acute lung injury induced by lipopolysaccharide (LPS), upregulation of
ADAM15
was observed in association with
pulmonary edema
and neutrophil infiltration. The LPS-induced inflammatory injury, as demonstrated by bronchoalveolar lavage neutrophil count, lung wet-to-dry weight ratio, and myeloperoxidase activity, was significantly attenuated in Adam15(-/-) mice. Studies with primary cell culture demonstrated abundant
ADAM15
expression in endothelial cells (ECs) of mouse lung but not in neutrophils. Deficiency of
ADAM15
in ECs had no obvious effect on basal permeability but significantly attenuated hyperpermeability response to LPS as evidenced by albumin flux assay and measurements of transendothelial electrical resistance, respectively.
ADAM15
deficiency also reduced neutrophil chemotactic transmigration across endothelial barriers in the presence or absence of formyl-methionyl-leucyl-phenylalanine (fMLP). Rescue expression of
ADAM15
in Adam15(-/-) ECs restored neutrophil transendothelial migration. These data indicate that
ADAM15
upregulation contributes to inflammatory lung injury by promoting endothelial hyperpermeability and neutrophil transmigration.
...
PMID:ADAM15 deficiency attenuates pulmonary hyperpermeability and acute lung injury in lipopolysaccharide-treated mice. 2316 86
