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.
authors: Program in Barrier Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. BarronL@niaid.nih.gov
authors: Luke
authors: L
authors: Barron
authors: Amber M
authors: AM
authors: Smith
authors: Karim C
authors: KC
authors: El Kasmi
authors: Joseph E
authors: JE
authors: Qualls
authors: Xiaozhu
authors: X
authors: Huang
authors: Allen
authors: A
authors: Cheever
authors: Lee A
authors: LA
authors: Borthwick
authors: Mark S
authors: MS
authors: Wilson
authors: Peter J
authors: PJ
authors: Murray
authors: Thomas A
authors: TA
authors: Wynn
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D001230:Aspergillus / Q000276:immunology; D015870:Gene Expression; D006099:Granuloma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D012550:Schistosoma mansoni / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; D010047:Ovalbumin; C544448:Arg1 protein, mouse; D001119:Arginase
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