Arginase 1 is expressed in myelocytes/metamyelocytes and localized in gelatinase granules of human neutrophils.
Arginase 1 (ARG1) metabolizes arginine, thus reducing the availability of arginine as a substrate for nitric oxide synthase (NOS). The decreased production of nitric oxide (NO) by NOS and the production of ornithine by ARG1 affect immune responses and tissue regeneration at sites of infection, respectively. We here demonstrate that ARG1 is synthesized in myelocytes/metamyelocytes and is stored in gelatinase granules. In accordance with this, activated neutrophils coreleased ARG1 and gelatinase to the extracellular environment on stimulation with phorbol-12-myristate 13-acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP), or tumor necrosis factor alpha (TNF-alpha). Overall, these findings define ARG1 as a genuine gelatinase granule protein and support a model in which activated neutrophils release ARG1 at sites of infection to modulate immune responses and promote tissue regeneration.
Jacobsen
Lars C
LC
Granulocyte Research Laboratory, Department of Hematology, Rigshospitalet University Hospital, Copenhagen, Denmark.
Theilgaard-Mönch
Kim
K
Christensen
Erik I
EI
Borregaard
Niels
N
D001119:Arginase / Q000235:genetics* / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000201:enzymology; D005089:Exocytosis; D018093:Gelatinases / Q000378:metabolism; D042381:Granulocyte Precursor Cells / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D018093:Gelatinases; D001119:Arginase; D013755:Tetradecanoylphorbol Acetate