title: Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity.
abstract: The balance of arginine metabolism via nitric oxide synthase (NOS) or arginase is an important determinant of the inflammatory response of murine macrophages and dendritic cells. Here we analyzed the expression of the isoform arginase I in human myeloid cells. Using healthy donors and patients with arginase I deficiency, we found that in human leukocytes arginase I is constitutively expressed only in granulocytes and is not modulated by a variety of proinflammatory and anti-inflammatory stimuli in vitro. We demonstrate that arginase I is localized in azurophil granules of neutrophils and constitutes a novel antimicrobial effector pathway, likely through arginine depletion in the phagolysosome. Our findings demonstrate important differences between murine and human leukocytes with respect to regulation and function of arginine metabolism via arginase.
authors.affiliation: Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. markus_munder@med.uni-heidelberg.de
authors.forename: Markus
authors.initials: M
authors.lastname: Munder
authors.forename: Faustino
authors.initials: F
authors.lastname: Mollinedo
authors.forename: Jero
authors.initials: J
authors.lastname: Calafat
authors.forename: Javier
authors.initials: J
authors.lastname: Canchado
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil-Lamaignere
authors.forename: José M
authors.initials: JM
authors.lastname: Fuentes
authors.forename: Claudia
authors.initials: C
authors.lastname: Luckner
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Doschko
authors.forename: Germán
authors.initials: G
authors.lastname: Soler
authors.forename: Klaus
authors.initials: K
authors.lastname: Eichmann
authors.forename: Frank-Michael
authors.initials: FM
authors.lastname: Müller
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Martin
authors.initials: M
authors.lastname: Goerner
authors.forename: Manuel
authors.initials: M
authors.lastname: Modolell
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism*; D001119:Arginase / Q000378:metabolism*; D001120:Arginine; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D020162:Hyperargininemia; D007527:Isoenzymes / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000648:ultrastructure; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009504:Neutrophils / Q000201:enzymology* / Q000648:ultrastructure; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000378:metabolism*; D010588:Phagosomes / Q000201:enzymology / Q000648:ultrastructure; D022142:Secretory Vesicles / Q000201:enzymology* / Q000648:ultrastructure; D013045:Species Specificity
chemical_list: D000935:Antifungal Agents; D007527:Isoenzymes; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase