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

L Barron, AM Smith, KC El Kasmi, JE Qualls, X Huang… - PloS one, 2013 - journals.plos.org
L Barron, AM Smith, KC El Kasmi, JE Qualls, X Huang, A Cheever, LA Borthwick, MS Wilson
PloS one, 2013journals.plos.org
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-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.
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