Leukocyte adam17 regulates acute pulmonary inflammation

Patrick G. Arndt, Brian Strahan, Yue Wang, Chunmei Long, Keisuke Horiuchi, Bruce Walcheck

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere19938
JournalPLoS One
Volume6
Issue number5
DOIs
Publication statusPublished - 2011

Fingerprint

L-Selectin
Chemokine CXCL5
leukocytes
Pneumonia
Chemokine CXCL1
Leukocytes
inflammation
lungs
neutrophils
Tropics
mice
Infiltration
Membrane Proteins
Peptide Hydrolases
Adhesion
Neutrophil Infiltration
Molecules
Substrates
Neutrophils
surface proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Arndt, P. G., Strahan, B., Wang, Y., Long, C., Horiuchi, K., & Walcheck, B. (2011). Leukocyte adam17 regulates acute pulmonary inflammation. PLoS One, 6(5), [e19938]. https://doi.org/10.1371/journal.pone.0019938

Leukocyte adam17 regulates acute pulmonary inflammation. / Arndt, Patrick G.; Strahan, Brian; Wang, Yue; Long, Chunmei; Horiuchi, Keisuke; Walcheck, Bruce.

In: PLoS One, Vol. 6, No. 5, e19938, 2011.

Research output: Contribution to journalArticle

Arndt, PG, Strahan, B, Wang, Y, Long, C, Horiuchi, K & Walcheck, B 2011, 'Leukocyte adam17 regulates acute pulmonary inflammation', PLoS One, vol. 6, no. 5, e19938. https://doi.org/10.1371/journal.pone.0019938
Arndt PG, Strahan B, Wang Y, Long C, Horiuchi K, Walcheck B. Leukocyte adam17 regulates acute pulmonary inflammation. PLoS One. 2011;6(5). e19938. https://doi.org/10.1371/journal.pone.0019938
Arndt, Patrick G. ; Strahan, Brian ; Wang, Yue ; Long, Chunmei ; Horiuchi, Keisuke ; Walcheck, Bruce. / Leukocyte adam17 regulates acute pulmonary inflammation. In: PLoS One. 2011 ; Vol. 6, No. 5.
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