Abstract
BackgroundArginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice.ResultsIn order to test the hypothesis that arginase has a role in allergic airway inflammation we generated arginase I-deficient bone marrow (BM) chimeric mice. Following transfer of arginase I-deficient BM into irradiated recipient mice, arginase I expression was not required for hematopoietic reconstitution and baseline immunity. Arginase I deficiency in bone marrow-derived cells decreased allergen-induced lung arginase by 85.8 ± 5.6%. In contrast, arginase II-deficient mice had increased lung arginase activity following allergen challenge to a similar level to wild type mice. BM-derived arginase I was not required for allergen-elicited sensitization, recruitment of inflammatory cells in the lung, and proliferation of cells. Furthermore, allergen-induced airway hyperresponsiveness and collagen deposition were similar in arginase-deficient and wild type mice. Additionally, arginase II-deficient mice respond similarly to their control wild type mice with allergen-induced inflammation, airway hyperresponsiveness, proliferation and collagen deposition.ConclusionBone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition.
Highlights
Arginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice
We demonstrate that arginase I expression does not affect bone marrow reconstitution following transfer into lethally irradiated recipients and that arginase is not required for baseline immunity
We demonstrate that bone marrow (BM)-derived arginase I is the main source of allergen-induced lung arginase
Summary
Arginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice. The pathophysiology of asthma is characterized by eosinophil-rich inflammatory cell infiltrates, increased mucus production, airway hyperreactivity, and reversible airway obstruction [3,4,5]. Experimentation in the asthma field has largely focused on analysis of the cellular and molecular events induced by allergen exposure in sensitized animals (primarily mice) and humans. While these studies have provided the rationale for the development of multiple therapeutic agents that interfere with specific inflammatory pathways [6], the development of the asthma phenotype is likely to be related to the complex interplay of a large number of additional genes, and their polymorphic variants
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