Submitted June 29, 2006
Accepted November 19, 2006
Arginase 1 is expressed in myelocytes/metamyelocytes and localized in gelatinase granules of human neutrophils
Lars C Jacobsen*, Kim Theilgaard-Moench, Erik I Christensen, and Niels Borregaard
The Granulocyte Research Laboratory, Department of Hematology, University Hospital, Copenhagen, Denmark
Department of Anatomy, University of Aarhus, Aarhus, Denmark
* Corresponding author; email: borregaard{at}rh.dk.
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 upon stimulation with phorbol-12-myristate 13-acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP), or tumor necrosis factor alpha (TNF-
).
Overall, these findings define ARG1 as a genuine gelatinase granule protein and support a model where activated neutrophils release ARG1 at sites of infection in order modulate immune responses and promote tissue regeneration.
