Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice.
BACKGROUND
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.


RESULTS
In 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.


CONCLUSIONS
Bone 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.
Niese
Kathryn A
KA
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Kathryn.Niese@cchmc.org
Collier
Ann R
AR
Hajek
Amanda R
AR
Cederbaum
Stephen D
SD
O'Brien
William E
WE
Wills-Karp
Marsha
M
Rothenberg
Marc E
ME
Zimmermann
Nives
N
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001119:Arginase / Q000276:immunology; D001854:Bone Marrow Cells / Q000201:enzymology* / Q000473:pathology; D016026:Bone Marrow Transplantation; D003094:Collagen / Q000378:metabolism; D020162:Hyperargininemia; D007114:Immunization; D007249:Inflammation; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011828:Radiation Chimera; D012130:Respiratory Hypersensitivity / Q000201:enzymology* / Q000473:pathology
D000485:Allergens; D003094:Collagen; C481673:Arg2 protein, mouse; D001119:Arginase