Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity.
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.
Munder
Markus
M
Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. markus_munder@med.uni-heidelberg.de
Mollinedo
Faustino
F
Calafat
Jero
J
Canchado
Javier
J
Gil-Lamaignere
Cristina
C
Fuentes
José M
JM
Luckner
Claudia
C
Doschko
Gwendolyn
G
Soler
Germán
G
Eichmann
Klaus
K
Müller
Frank-Michael
FM
Ho
Anthony D
AD
Goerner
Martin
M
Modolell
Manuel
M
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
D000935:Antifungal Agents; D007527:Isoenzymes; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase