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Fast and Specific Assessment of the Halogenating Peroxidase Activity in Leukocyte-enriched Blood Samples
Published on: July 28, 2016
Human eosinophil granulocytes do not express the enzyme arginase
Claudia Luckner-Minden1, Ina Fischer, Claus-Dieter Langhans
1Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Abstract:
Human polymorphonuclear PMN constitutively express the enzyme arginase I, which hydrolyzes arginine to ornithine and urea. This arginine consumption has been recognized as a key pathway of myeloid cell-mediated suppression of the adaptive immune system during inflammation, infection, and tumor growth. Eos granulocytes are crucial immunoregulatory and effector cells of allergic inflammation and infections with parasites and helminths and in a variety of tumors. Here, we analyzed if human Eos also express arginase with its potential immunosuppressive consequences. We show that human peripheral blood Eos do not express arginase I or II protein or arginase enzymatic activity. Correspondingly, no metabolism of arginine to ornithine can be detected in Eos-S. Neither Eos apoptosis nor cytokine-mediated cellular activation induces arginase in human Eos in vitro. Finally, we show that arginase activity and protein are also undetectable in Eos of allergic patients from peripheral blood or from BALF activated in vivo during allergic pulmonary inflammation. This work demonstrates a fundamental difference between neutrophil and Eos granulocytes. As Eos are not equipped with the immunosuppressive enzyme arginase, they cannot participate, via arginine limitation, in the suppression of the evolving adaptive immune response in allergy, infections, or tumor immunity.
Insights
Human eosinophils (Eos) do not express the immunosuppressive enzyme arginase. Unlike neutrophils, Eos cannot limit arginine, impacting immune responses in allergies, infections, and tumors.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Human polymorphonuclear cells (PMNs) express arginase I, suppressing adaptive immunity by consuming arginine.
- Eosinophils (Eos) are key immune cells in allergic inflammation, parasitic infections, and tumor immunity.
- The role of arginase in Eos function and immune modulation remains unclear.
Purpose of the Study:
- To investigate whether human Eos express arginase and if its activity has immunosuppressive consequences.
- To determine if Eos contribute to arginine metabolism in the context of immune responses.
Main Methods:
- Analysis of arginase I and II protein expression in human peripheral blood Eos.
- Assay for arginase enzymatic activity in Eos.
- Detection of arginine metabolism to ornithine in Eos.
- In vitro studies involving Eos apoptosis and cytokine activation.
- Examination of Eos from allergic patients (peripheral blood and bronchoalveolar lavage fluid).
Main Results:
- Human peripheral blood Eos lack arginase I and II protein and enzymatic activity.
- No arginine metabolism to ornithine was detected in Eos.
- Eos apoptosis or cytokine activation did not induce arginase expression.
- Arginase was undetectable in Eos from allergic patients, even during in vivo inflammation.
Conclusions:
- Human Eos fundamentally differ from neutrophils regarding arginase expression.
- Eos do not possess the immunosuppressive enzyme arginase.
- Eos cannot suppress adaptive immune responses through arginine limitation in allergic inflammation, infections, or tumor immunity.
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