JOURNAL ARTICLE

Leukocyte ADAM17 regulates acute pulmonary inflammation

Patrick G Arndt, Brian Strahan, Yue Wang, Chunmei Long, Keisuke Horiuchi, Bruce Walcheck
PloS One 2011, 6 (5): e19938
21603616
The transmembrane protease ADAM17 regulates the release and density of various leukocyte cell surface proteins that modulate inflammation, including L-selectin, TNF-α, and IL-6R. At this time, its in vivo substrates and role in pulmonary inflammation have not been directly examined. Using conditional ADAM17 knock-out mice, we investigated leukocyte ADAM17 in acute lung inflammation. Alveolar TNF-α levels were significantly reduced (>95%) in ADAM17-null mice following LPS administration, as was the shedding of L-selectin, a neutrophil-expressed adhesion molecule. Alveolar IL-6R levels, however, were reduced by only ≈25% in ADAM17-null mice, indicating that ADAM17 is not its primary sheddase in our model. Neutrophil infiltration into the alveolar compartment is a key event in the pathophysiology of acute airway inflammation. Following LPS inhalation, alveolar neutrophil levels and lung inflammation in ADAM17-null mice were overall reduced when compared to control mice. Interestingly, however, neutrophil recruitment to the alveolar compartment occurred earlier in ADAM17-null mice after exposure to LPS. This decrease in alveolar neutrophil recruitment in ADAM17-null mice was accompanied by significantly diminished alveolar levels of the neutrophil-tropic chemokines CXCL1 and CXCL5. Altogether, our study suggests that leukocyte ADAM17 promotes inflammation in the lung, and thus this sheddase may be a potential target in the design of pharmacologic therapies for acute lung injury.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
21603616
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"