{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T13:08:50Z","timestamp":1771679330143,"version":"3.50.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T00:00:00Z","timestamp":1407369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["MU1547\/3-1"],"award-info":[{"award-number":["MU1547\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,8,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Arginine depletion via myeloid cell arginase is critically involved in suppression of the adaptive immune system during cancer or chronic inflammation. On the other hand, arginine depletion is being developed as a novel anti-tumor metabolic strategy to deprive arginine-auxotrophic cancer cells of this amino acid. In human immune cells, arginase is mainly expressed constitutively in PMNs. We therefore purified human primary PMNs from healthy donors and analyzed PMN function as the main innate effector cell and arginase producer in the context of arginine deficiency. We demonstrate that human PMN viability, activation-induced IL-8 synthesis, chemotaxis, phagocytosis, generation of ROS, and fungicidal activity are not impaired by the absence of arginine in vitro. Also, profound pharmacological arginine depletion in vivo via ADI-PEG20 did not inhibit PMN functions in a mouse model of pulmonary invasive aspergillosis; PMN invasion into the lung, activation, and successful PMN-dependent clearance of Aspergillus fumigatus and survival of mice were not impaired. These novel findings add to a better understanding of immunity during inflammation-associated arginine depletion and are also important for the development of therapeutic arginine depletion as anti-metabolic tumor therapy.<\/jats:p>","DOI":"10.1189\/jlb.3ab0214-082r","type":"journal-article","created":{"date-parts":[[2014,8,8]],"date-time":"2014-08-08T06:20:12Z","timestamp":1407478812000},"page":"1047-1053","source":"Crossref","is-referenced-by-count":17,"title":["Granulocyte functions are independent of arginine availability"],"prefix":"10.1093","volume":"96","author":[{"given":"Katharina","family":"Kapp","sequence":"first","affiliation":[{"name":"Institute of Immunology, University of Heidelberg , Germany"},{"name":"Department of Neonatology, University Children's Hospital , Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Pr\u00fcfer","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Medical Center of the Johannes Gutenberg University , Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian S","family":"Michel","sequence":"additional","affiliation":[{"name":"Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University , Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Habermeier","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University Medical Center of the Johannes Gutenberg University , Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Luckner-Minden","sequence":"additional","affiliation":[{"name":"Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University , Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Giese","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University of Heidelberg , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Bomalaski","sequence":"additional","affiliation":[{"name":"Polaris Pharmaceuticals , San Diego, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus-Dieter","family":"Langhans","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, University Children's Hospital , Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascale","family":"Kropf","sequence":"additional","affiliation":[{"name":"Section of Immunology, Department of Medicine, Imperial College , London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Section of Immunology, Department of Medicine, Imperial College , London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen I","family":"Closs","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University Medical Center of the Johannes Gutenberg University , Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus P","family":"Radsak","sequence":"additional","affiliation":[{"name":"Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University , Mainz, Germany"},{"name":"Research Center for Immunology, University Medical Center of the Johannes Gutenberg University , Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Munder","sequence":"additional","affiliation":[{"name":"Department of Neonatology, University Children's Hospital , Heidelberg, Germany"},{"name":"Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University , Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,8,7]]},"reference":[{"key":"2023032708364934200_","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.immuni.2010.11.011","article-title":"Neutrophils, from marrow to microbes","volume":"33","author":"Borregaard","year":"2010","journal-title":"Immunity"},{"key":"2023032708364934200_","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nri3024","article-title":"Neutrophils in the activation and regulation of innate and adaptive immunity","volume":"11","author":"Mantovani","year":"2011","journal-title":"Nat. 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