Constitutive expression of IL-2Rbeta chain and its effects on IL-2-induced vascular leak syndrome
| Autor: | José Roberto Lapa e Silva, Jacques Thèze, Jean Lefort, B. Boris Vargaftig, Eric Assier, Jean-Louis Moreau, Valérie Jullien |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Genetically modified mouse Neutrophils Transgene medicine.medical_treatment Immunology Gene Expression Cell Count Mice Transgenic Biology Biochemistry Mice Cell Movement In vivo Edema medicine Animals Humans Immunology and Allergy Lymphocytes Receptor Lung Molecular Biology Methacholine Chloride Peroxidase Plethysmography Whole Body medicine.diagnostic_test Airway Resistance Wild type Proteins Receptors Interleukin-2 Organ Size Hematology Interleukin-2 Receptor beta Subunit Mice Inbred C57BL Bronchoalveolar lavage Cytokine Interleukin-2 medicine.symptom Bronchoalveolar Lavage Fluid Capillary Leak Syndrome |
| Zdroj: | Cytokine. 32:280-286 |
| ISSN: | 1043-4666 |
| DOI: | 10.1016/j.cyto.2005.10.006 |
| Popis: | IL-2-induced vascular leak syndrome (VLS) is an important mechanism explaining the toxic effects of this cytokine and limiting its therapeutic use. We previously characterized a mouse model of IL-2-induced pulmonary VLS used to demonstrate that NK lymphocytes are involved in early/acute phase VLS (after one IL-2 injection). We also showed that NK cells and polymorphonuclear neutrophils (PMN) are involved in the late/chronic phase of the syndrome (after four daily IL-2 injections). In this study we use our mouse model to evaluate the role played by the IL-2 receptor (IL-2R) in VLS induction. Mouse and human IL-2R are different since the mouse IL-2Rbeta chain does not recognize IL-2. Here, we compare the acute and late VLS responses in human IL-2Rbeta transgenic and C57BL/6 wild type mice. Parameters linked to early phase VLS (bronchoconstriction and PMN mobilization) are enhanced in human IL-2Rbeta transgenic mice. By contrast, parameters used to measure late events (protein leakage and edema) are similar in human IL-2Rbeta transgenic mice and C57BL/6 wild type animals. However, after four IL-2 injections, the cellular content of the bronchoalveolar lavage fluids was different between the two types of animals. This study also characterizes a humanized animal model that could be further used to study human IL-2 activity and side effects in vivo. |
| Databáze: | OpenAIRE |
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