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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2549-2556.
Prepublished online as a Blood First Edition Paper on November 16, 2004; DOI 10.1182/blood-2004-07-2521.
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Submitted July 2, 2004
Accepted November 9, 2004
Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity
Markus Munder*, Faustino Mollinedo, Jero Calafat, Javier Canchado, Cristina Gil-Lamaignere, Jose M Fuentes, Claudia Luckner, Gwendolyn Doschko, German Soler, Klaus Eichmann, Frank-Michael Muller, Anthony D Ho, Martin Goerner, and Manuel Modolell
Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Molecular Hematology and Oncology, German Cancer Research Center, Heidelberg, Germany; Institute of Immunology, University of Heidelberg, Heidelberg, Germany
Centro de Investigacion del Cancer, Instituto de Biologia Molecular y Celular del Cancer, CSIC-Universidad de Salamanca, Salamanca, Spain
Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands
Section of Pediatric Pulmonology and Infectious Diseases, IIIrd Department of Pediatrics, Children's Hospital, University of Heidelberg, Heidelberg, Germany
Departamento de Bioquimica y Biologia Molecular, E.U. Enfermeria y T.O., Universidad de Extremadura, Caceres, Spain
Clinical Cooperation Unit Molecular Hematology and Oncology, German Cancer Research Center, Heidelberg, Germany
Departamento de Bioquimica y Biologia Molecular, Facultad de Veterinaria, Universidad de Extremadura, Caceres, Spain
Department of Cellular Immunology, Max-Planck-Institute for Immunobiology, Freiburg, Germany
Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany
Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Molecular Hematology and Oncology, German Cancer Research Center, Heidelberg, Germany
* Corresponding author; email: Markus.Munder{at}urz.uni-heidelberg.de.
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 analysed the expression of the isoform arginase I in human myeloid cells. Using healthy donors and arginase I-deficient patients, we found that in human leukocytes arginase I is constitutively expressed only in granulocytes and is not modulated by a variety of pro- and antiinflammatory stimuli in vitro. We demonstrate that arginase I is localised 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.
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