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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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PHAGOCYTES

Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity

Markus Munder, Faustino Mollinedo, Jero Calafat, Javier Canchado, Cristina Gil-Lamaignere, José M. Fuentes, Claudia Luckner, Gwendolyn Doschko, Germán Soler, Klaus Eichmann, Frank-Michael Müller, Anthony D. Ho, Martin Goerner, and Manuel Modolell

From the 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 Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, 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 Bioquímica y Biología Molecular, E.U. Enfermería y T.O., Universidad de Extremadura, Cáceres, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad de Extremadura, Cáceres, Spain; and Department of Cellular Immunology, Max-Planck Institute for Immunobiology, Freiburg, Germany.

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.


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