Transcript synthesis and surface expression of the interleukin-2 receptor (alpha-, beta-, and gamma-chain) by normal and malignant myeloid cells
| Autor: | HJ Gruss, Jerome Ritz, JC Renauld, M. A. Brach, Friedhelm Herrmann, C Kirschning, U von Arnim, T Nakarai, Wolf-Dieter Ludwig, Leonid Karawajew, Ralf R. Schumann |
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| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Myeloid Janus kinase 3 Immunology Myeloid leukemia Cell Biology Hematology Biology medicine.disease Biochemistry Molecular biology Leukemia Endocrinology medicine.anatomical_structure Cell surface receptor Internal medicine medicine Myelopoiesis Signal transduction Interleukin-7 receptor |
| Zdroj: | Blood. 87:2419-2427 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Expression of the interleukin-2 receptor alpha-(IL-2Ralpha-), IL-2Rbeta- , and the recently identified IL-2Rgamma-chain was examined on a wide range of cells of myeloid origin including neutrophils, monocytes, normal bone marrow-derived myeloid progenitors enriched for CD34+ cells, bone marrow blasts obtained from acute myelogenous leukemia (AML) patients, and permanent myeloid leukemia cell lines by reverse transcriptase-polymerase chain reaction and surface membrane analysis using receptor chain-specific monoclonal antibodies and flow cytometry. Expression of the p75 IL-2Rbeta- and the p64 IL-2Rgamma-chain was a common finding in most of the myeloid cell samples investigated, whereas IL-2Ralpha-chain was less frequently expressed. Although the high-affinity IL-2R form (ie, the alpha+, beta+, gamma+ IL-2R form) was detectable in a small minority of primary AML samples as well as the KG- 1 cell line and IL-2 binding to these cells was sufficient to initiate signal transduction as evidenced by an increase in overall protein tyrosine phosphorylation and more specifically in tyrosine phosphorylation of the Janus kinase (JAK) 3, in none of these cell types did exposure to IL-2 affect cell growth kinetics. These results suggest that, in myeloid cells, the IL-2R may not stimulate mitogenic responses or that its components may be expressed in a combinational association with receptors for other cytokines and that IL-2Rgamma may play a regulatory role in normal and malignant myelopoiesis possibly independent from IL-2. Because recent studies by others have indicated that the IL-2Rgamma- chain may be shared by the IL-4R, the IL-7R, and most likely the IL-9R, expression of mRNA of these receptor types was also investigated in these cell samples. Surprisingly, in a substantial part of the myeloid lineage cells examined, an IL-2Rgamma+, IL-4R-, IL7R- configuration was noted that was, however, frequently associated with expression of IL-9R. Sharing of IL-9R/IL-2R components was furthermore suggested by inhibition of 125I-IL-2 binding to primary AML cells with excess of unlabeled IL-9. |
| Databáze: | OpenAIRE |
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