Role of Arginase 1 from Myeloid Cells in Th2-Dominated Lung Inflammation

Luke Barron, Amber Smith, Karim C. El Kasmi, Joseph E. Qualls, Xiaozhu Huang, Allen Cheever, Lee A. Borthwick, Mark S. Wilson, Peter J. Murray, Thomas A. Wynn

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Th2-driven lung inflammation increases Arginase 1 (Arg1) expression in alternatively-activated macrophages (AAMs). AAMs modulate T cell and wound healing responses and Arg1 might contribute to asthma pathogenesis by inhibiting nitric oxide production, regulating fibrosis, modulating arginine metabolism and restricting T cell proliferation. We used mice lacking Arg1 in myeloid cells to investigate the contribution of Arg1 to lung inflammation and pathophysiology. In six model systems encompassing acute and chronic Th2-mediated lung inflammation we observed neither a pathogenic nor protective role for myeloid-expressed Arg1. The number and composition of inflammatory cells in the airways and lungs, mucus secretion, collagen deposition, airway hyper-responsiveness, and T cell cytokine production were not altered if AAMs were deficient in Arg1 or simultaneously in both Arg1 and NOS2. Our results argue that Arg1 is a general feature of alternative activation but only selectively regulates Th2 responses. Therefore, attempts to experimentally or therapeutically inhibit arginase activity in the lung should be examined with caution.

Original languageEnglish (US)
Article numbere61961
JournalPloS one
Volume8
Issue number4
DOIs
StatePublished - Apr 24 2013

Fingerprint

Arginase
arginase
Myeloid Cells
Pneumonia
inflammation
lungs
T-cells
Macrophages
cells
macrophages
T-lymphocytes
T-Lymphocytes
Respiratory Hypersensitivity
Lung
Mucus
Cell proliferation
asthma
Wound Healing
pathophysiology
tissue repair

All Science Journal Classification (ASJC) codes

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

Cite this

Barron, L., Smith, A., El Kasmi, K. C., Qualls, J. E., Huang, X., Cheever, A., ... Wynn, T. A. (2013). Role of Arginase 1 from Myeloid Cells in Th2-Dominated Lung Inflammation. PloS one, 8(4), [e61961]. https://doi.org/10.1371/journal.pone.0061961

Role of Arginase 1 from Myeloid Cells in Th2-Dominated Lung Inflammation. / Barron, Luke; Smith, Amber; El Kasmi, Karim C.; Qualls, Joseph E.; Huang, Xiaozhu; Cheever, Allen; Borthwick, Lee A.; Wilson, Mark S.; Murray, Peter J.; Wynn, Thomas A.

In: PloS one, Vol. 8, No. 4, e61961, 24.04.2013.

Research output: Contribution to journalArticle

Barron, L, Smith, A, El Kasmi, KC, Qualls, JE, Huang, X, Cheever, A, Borthwick, LA, Wilson, MS, Murray, PJ & Wynn, TA 2013, 'Role of Arginase 1 from Myeloid Cells in Th2-Dominated Lung Inflammation', PloS one, vol. 8, no. 4, e61961. https://doi.org/10.1371/journal.pone.0061961
Barron L, Smith A, El Kasmi KC, Qualls JE, Huang X, Cheever A et al. Role of Arginase 1 from Myeloid Cells in Th2-Dominated Lung Inflammation. PloS one. 2013 Apr 24;8(4). e61961. https://doi.org/10.1371/journal.pone.0061961
Barron, Luke ; Smith, Amber ; El Kasmi, Karim C. ; Qualls, Joseph E. ; Huang, Xiaozhu ; Cheever, Allen ; Borthwick, Lee A. ; Wilson, Mark S. ; Murray, Peter J. ; Wynn, Thomas A. / Role of Arginase 1 from Myeloid Cells in Th2-Dominated Lung Inflammation. In: PloS one. 2013 ; Vol. 8, No. 4.
@article{5a3b162ba7a44a008233ef12fb1109f3,
title = "Role of Arginase 1 from Myeloid Cells in Th2-Dominated Lung Inflammation",
abstract = "Th2-driven lung inflammation increases Arginase 1 (Arg1) expression in alternatively-activated macrophages (AAMs). AAMs modulate T cell and wound healing responses and Arg1 might contribute to asthma pathogenesis by inhibiting nitric oxide production, regulating fibrosis, modulating arginine metabolism and restricting T cell proliferation. We used mice lacking Arg1 in myeloid cells to investigate the contribution of Arg1 to lung inflammation and pathophysiology. In six model systems encompassing acute and chronic Th2-mediated lung inflammation we observed neither a pathogenic nor protective role for myeloid-expressed Arg1. The number and composition of inflammatory cells in the airways and lungs, mucus secretion, collagen deposition, airway hyper-responsiveness, and T cell cytokine production were not altered if AAMs were deficient in Arg1 or simultaneously in both Arg1 and NOS2. Our results argue that Arg1 is a general feature of alternative activation but only selectively regulates Th2 responses. Therefore, attempts to experimentally or therapeutically inhibit arginase activity in the lung should be examined with caution.",
author = "Luke Barron and Amber Smith and {El Kasmi}, {Karim C.} and Qualls, {Joseph E.} and Xiaozhu Huang and Allen Cheever and Borthwick, {Lee A.} and Wilson, {Mark S.} and Murray, {Peter J.} and Wynn, {Thomas A.}",
year = "2013",
month = "4",
day = "24",
doi = "10.1371/journal.pone.0061961",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Role of Arginase 1 from Myeloid Cells in Th2-Dominated Lung Inflammation

AU - Barron, Luke

AU - Smith, Amber

AU - El Kasmi, Karim C.

AU - Qualls, Joseph E.

AU - Huang, Xiaozhu

AU - Cheever, Allen

AU - Borthwick, Lee A.

AU - Wilson, Mark S.

AU - Murray, Peter J.

AU - Wynn, Thomas A.

PY - 2013/4/24

Y1 - 2013/4/24

N2 - Th2-driven lung inflammation increases Arginase 1 (Arg1) expression in alternatively-activated macrophages (AAMs). AAMs modulate T cell and wound healing responses and Arg1 might contribute to asthma pathogenesis by inhibiting nitric oxide production, regulating fibrosis, modulating arginine metabolism and restricting T cell proliferation. We used mice lacking Arg1 in myeloid cells to investigate the contribution of Arg1 to lung inflammation and pathophysiology. In six model systems encompassing acute and chronic Th2-mediated lung inflammation we observed neither a pathogenic nor protective role for myeloid-expressed Arg1. The number and composition of inflammatory cells in the airways and lungs, mucus secretion, collagen deposition, airway hyper-responsiveness, and T cell cytokine production were not altered if AAMs were deficient in Arg1 or simultaneously in both Arg1 and NOS2. Our results argue that Arg1 is a general feature of alternative activation but only selectively regulates Th2 responses. Therefore, attempts to experimentally or therapeutically inhibit arginase activity in the lung should be examined with caution.

AB - Th2-driven lung inflammation increases Arginase 1 (Arg1) expression in alternatively-activated macrophages (AAMs). AAMs modulate T cell and wound healing responses and Arg1 might contribute to asthma pathogenesis by inhibiting nitric oxide production, regulating fibrosis, modulating arginine metabolism and restricting T cell proliferation. We used mice lacking Arg1 in myeloid cells to investigate the contribution of Arg1 to lung inflammation and pathophysiology. In six model systems encompassing acute and chronic Th2-mediated lung inflammation we observed neither a pathogenic nor protective role for myeloid-expressed Arg1. The number and composition of inflammatory cells in the airways and lungs, mucus secretion, collagen deposition, airway hyper-responsiveness, and T cell cytokine production were not altered if AAMs were deficient in Arg1 or simultaneously in both Arg1 and NOS2. Our results argue that Arg1 is a general feature of alternative activation but only selectively regulates Th2 responses. Therefore, attempts to experimentally or therapeutically inhibit arginase activity in the lung should be examined with caution.

UR - http://www.scopus.com/inward/record.url?scp=84876586281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876586281&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0061961

DO - 10.1371/journal.pone.0061961

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e61961

ER -