PMID- 23161886
OWN - NLM
STAT- MEDLINE
DCOM- 20130326
LR  - 20211021
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 304
IP  - 3
DP  - 2013 Feb 1
TI  - ADAM15 deficiency attenuates pulmonary hyperpermeability and acute lung injury in 
      lipopolysaccharide-treated mice.
PG  - L135-42
LID - 10.1152/ajplung.00133.2012 [doi]
AB  - 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.
FAU - Sun, Chongxiu
AU  - Sun C
AD  - Department of Molecular Pharmacology and Physiology, University of South Florida 
      Morsani College of Medicine, Tampa, FL 33612, USA.
FAU - Beard, Richard S Jr
AU  - Beard RS Jr
FAU - McLean, Danielle L
AU  - McLean DL
FAU - Rigor, Robert R
AU  - Rigor RR
FAU - Konia, Thomas
AU  - Konia T
FAU - Wu, Mack H
AU  - Wu MH
FAU - Yuan, Sarah Y
AU  - Yuan SY
LA  - eng
GR  - R01 HL096640/HL/NHLBI NIH HHS/United States
GR  - HL61507/HL/NHLBI NIH HHS/United States
GR  - HL96640/HL/NHLBI NIH HHS/United States
GR  - HL84542/HL/NHLBI NIH HHS/United States
GR  - R01 GM097270/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121116
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Proteins)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Adam15 protein, mouse)
SB  - IM
MH  - ADAM Proteins/deficiency/*genetics
MH  - Acute Lung Injury/chemically induced/genetics/*metabolism/pathology
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid/cytology
MH  - Electric Impedance
MH  - Endothelial Cells/*metabolism/pathology
MH  - Lipopolysaccharides/pharmacology
MH  - Lung/*metabolism/pathology
MH  - Membrane Proteins/deficiency/*genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Neutrophil Infiltration
MH  - Neutrophils/*metabolism/pathology
MH  - Permeability
MH  - Peroxidase/genetics/metabolism
MH  - Primary Cell Culture
MH  - Pulmonary Edema/chemically induced/genetics/*metabolism/pathology
MH  - Transendothelial and Transepithelial Migration
MH  - Up-Regulation
PMC - PMC3567368
EDAT- 2012/11/20 06:00
MHDA- 2013/03/27 06:00
PMCR- 2014/02/01
CRDT- 2012/11/20 06:00
PHST- 2012/11/20 06:00 [entrez]
PHST- 2012/11/20 06:00 [pubmed]
PHST- 2013/03/27 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - ajplung.00133.2012 [pii]
AID - L-00133-2012 [pii]
AID - 10.1152/ajplung.00133.2012 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2013 Feb 1;304(3):L135-42. doi: 
      10.1152/ajplung.00133.2012. Epub 2012 Nov 16.