Journal of Experimental Medicine, Vol 181, 889-899, Copyright © 1995 by Rockefeller University Press

ARTICLES

Multi-colony stimulating activity of interleukin 5 (IL-5) on hematopoietic progenitors from transgenic mice that express IL-5 receptor alpha subunit constitutively

M Takagi, T Hara, M Ichihara, K Takatsu and A Miyajima
Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304.

The interleukin 3 (IL-3), IL-5, and granulocyte/macrophage colony- stimulating factor receptors consist of a cytokine-specific alpha subunit and the common beta subunit. Whereas IL-3 stimulates various lineages of hematopoietic cells, including multipotential progenitors, IL-5 acts mainly as an eosinophil lineage-specific factor. To investigate whether the lineage specificity of IL-5 is due to restricted expression of the IL-5 receptor alpha subunit (IL-5R alpha), we generated transgenic mice that express the mouse IL-5R alpha constitutively by phosphoglycerate kinase promoter. The transgenic mouse expressed IL-5R alpha ubiquitously, and the bone marrow cells formed various types of colonies, including multi-lineage colonies, in response to IL-5. IL-5 also supported formation of both multi-lineage and blast cell colonies from dormant progenitors of the 5-fluorouracil- treated transgenic mice. The cells composing the blast cell colony gave rise to many colonies including multi-lineage colonies when they were replated in secondary culture containing either Il-5 or IL-3. There was no significant difference in replating efficiency or in types of secondary colonies between IL-5- and IL-3-stimulated cultures. Conversely, the cells from the IL-3-induced blast cell colonies of the transgenic mice proliferated in response to either IL-3 or IL-5. Thus, the development of the progenitors can be equally supported by either IL-5 or IL-3, suggesting that intracellular signals from the IL-3R can be replaced by those from IL-5. These results strongly suggest that the lineage specificity of IL-5 is mainly due to the restricted expression of IL-5R alpha.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Iwasaki, H., Mizuno, S.-i., Mayfield, R., Shigematsu, H., Arinobu, Y., Seed, B., Gurish, M. F., Takatsu, K., Akashi, K. (2005). Identification of eosinophil lineage-committed progenitors in the murine bone marrow. J. Exp. Med. 201: 1891-1897 [Abstract] [Full Text]  
• Iwasaki-Arai, J., Iwasaki, H., Miyamoto, T., Watanabe, S., Akashi, K. (2003). Enforced Granulocyte/Macrophage Colony-stimulating Factor Signals Do Not Support Lymphopoiesis, but Instruct Lymphoid to Myelomonocytic Lineage Conversion. J. Exp. Med. 197: 1311-1322 [Abstract] [Full Text]  
• Watanabe, S., Aoki, Y., Nishijima, I., Xu, M.-j., Arai, K.-i. (2000). Analysis of Signals and Functions of the Chimeric Human Granuloctye-Macrophage Colony-Stimulating Factor Receptor in BA/F3 Cells and Transgenic Mice. J. Immunol. 164: 3635-3644 [Abstract] [Full Text]  
• Takagi, M., Nakamura, T., Sawada, T., Kaneko, A., Nozaki-Ukai, M., Nakahata, T., Yokota, T., Heike, T. (1999). Chimeric Cytokine Receptor Can Transduce Expansion Signals in Interleukin 6 Receptor alpha (IL-6Ralpha )-, IL-11Ralpha -, and gp130-low to -negative Primitive Hematopoietic Progenitors. Mol. Biol. Cell 10: 3633-3642 [Abstract] [Full Text]  
• Yang, F.-C., Tsuji, K., Oda, A., Ebihara, Y., Xu, M.-j., Kaneko, A., Hanada, S., Mitsui, T., Kikuchi, A., Manabe, A., Watanabe, S., Ikeda, Y., Nakahata, T. (1999). Differential Effects of Human Granulocyte Colony-Stimulating Factor (hG-CSF) and Thrombopoietin on Megakaryopoiesis and Platelet Function in hG-CSF Receptor-Transgenic Mice. Blood 94: 950-958 [Abstract] [Full Text]  
• Iwama, A., Pan, J., Zhang, P., Reith, W., Mach, B., Tenen, D. G., Sun, Z. (1999). Dimeric RFX Proteins Contribute to the Activity and Lineage Specificity of the Interleukin-5 Receptor alpha  Promoter through Activation and Repression Domains. Mol. Cell. Biol. 19: 3940-3950 [Abstract] [Full Text]  
• Yang, F.-C., Watanabe, S., Tsuji, K., Xu, M.-j., Kaneko, A., Ebihara, Y., Nakahata, T. (1998). Human Granulocyte Colony-Stimulating Factor (G-CSF) Stimulates the In Vitro and In Vivo Development But Not Commitment of Primitive Multipotential Progenitors From Transgenic Mice Expressing the Human G-CSF Receptor. Blood 92: 4632-4640 [Abstract] [Full Text]  
• Wang, P., Wu, P., Cheewatrakoolpong, B., Myers, J. G., Egan, R. W., Billah, M. M. (1998). Selective Inhibition of IL-5 Receptor {alpha}-Chain Gene Transcription by IL-5, IL-3, and Granulocyte-Macrophage Colony-Stimulating Factor in Human Blood Eosinophils. J. Immunol. 160: 4427-4432 [Abstract] [Full Text]  
• Pierce, A, Whetton, A., Owen-Lynch, P., Tavernier, J, Spooncer, E, Dexter, T., Heyworth, C. (1998). Ectopic interleukin-5 receptor expression promotes proliferation without development in a multipotent hematopoietic cell line. J. Cell Sci. 111: 815-823 [Abstract]  
• Nishijima, I., Nakahata, T., Watanabe, S., Tsuji, K., Tanaka, I., Hirabayashi, Y., Inoue, T., Arai, K. (1997). Hematopoietic and Lymphopoietic Responses in Human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF ) Receptor Transgenic Mice Injected With Human GM-CSF. Blood 90: 1031-1038 [Abstract] [Full Text]  
• Hara, T, Miyajima, A (1996). Function and signal transduction mediated by the interleukin 3 receptor system in hematopoiesis. Stem Cells 14: 605-618 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS