Role of arginase 1 from myeloid cells in th2-dominated lung inflammation

PLoS One. 2013 Apr 24;8(4):e61961. doi: 10.1371/journal.pone.0061961. Print 2013.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Helminth / immunology
  • Arginase / genetics
  • Arginase / metabolism*
  • Aspergillus / immunology
  • Gene Expression
  • Granuloma / immunology
  • Granuloma / metabolism
  • Granuloma / pathology
  • Macrophage Activation / genetics
  • Macrophage Activation / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism*
  • Myeloid Cells / pathology
  • Ovalbumin / immunology
  • Pneumonia / genetics
  • Pneumonia / immunology*
  • Pneumonia / metabolism*
  • Pneumonia / pathology
  • Schistosoma mansoni / immunology
  • Th2 Cells / immunology*


  • Antigens, Helminth
  • Ovalbumin
  • Arg1 protein, mouse
  • Arginase