PMID- 17119118 OWN - NLM STAT- MEDLINE DCOM- 20070531 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 109 IP - 7 DP - 2007 Apr 1 TI - Arginase 1 is expressed in myelocytes/metamyelocytes and localized in gelatinase granules of human neutrophils. PG - 3084-7 AB - 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. FAU - Jacobsen, Lars C AU - Jacobsen LC AD - Granulocyte Research Laboratory, Department of Hematology, Rigshospitalet University Hospital, Copenhagen, Denmark. FAU - Theilgaard-Monch, Kim AU - Theilgaard-Monch K FAU - Christensen, Erik I AU - Christensen EI FAU - Borregaard, Niels AU - Borregaard N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Tumor Necrosis Factor-alpha) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - EC 3.4.24.- (Gelatinases) RN - EC 3.5.3.1 (Arginase) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Arginase/*genetics/*metabolism MH - Cytoplasmic Granules/enzymology MH - Exocytosis MH - Gelatinases/metabolism MH - Granulocyte Precursor Cells/*enzymology MH - Humans MH - In Vitro Techniques MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Neutrophils/drug effects/*enzymology MH - Tetradecanoylphorbol Acetate/pharmacology MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 2006/11/23 09:00 MHDA- 2007/06/01 09:00 CRDT- 2006/11/23 09:00 PHST- 2006/11/23 09:00 [pubmed] PHST- 2007/06/01 09:00 [medline] PHST- 2006/11/23 09:00 [entrez] AID - S0006-4971(20)41817-8 [pii] AID - 10.1182/blood-2006-06-032599 [doi] PST - ppublish SO - Blood. 2007 Apr 1;109(7):3084-7. doi: 10.1182/blood-2006-06-032599.