Arginase-1 and Ym1 Are Markers for Murine, but Not Human, Alternatively Activated Myeloid Cells
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免疫学杂志 2005年第11期
In an interesting paper, Scotton et al. (1) reported the effects of IL-13 on the transcriptional profile of human monocytes. Comparing their results with studies analyzing the profile induced by IL-4 in murine macrophages (2, 3), the authors notice some differences, giving as examples up-regulation of Ym1 and arginase-1 in murine macrophages, but not in human monocytes. The authors suggest these differences reflect the fact that IL-4 and IL-13 are highly similar, yet different molecules. Besides overlapping effects with IL-4, IL-13 indeed has documented nonredundant functions and effects (4, 5). However, when comparing results obtained in murine macrophages to human monocytes, differences between monocytes and differentiated macrophages, as well as interspecies differences, may be involved. Indeed, human monocytes and monocyte-derived macrophages exhibit differences in their response to IL-4 and IL-13 (6). Moreover, we and others recently documented that, similar to IL-13, IL-4 does not induce arginase-1 in human monocytes and monocyte-derived macrophages (7, 8), in contrast to murine macrophages, where the arginine metabolism is even one of the discriminative criteria between so-called alternatively and classically activated macrophages (9). Furthermore, in human monocytes, under conditions inducing mannose receptor and macrophage galactose-type C-type lectin, markers for IL-4/IL-13-induced, alternatively activated macrophages (7), we have not detected induction by IL-4 and IL-13 of eosinophil chemotactic cytokine, the closest human homolog of mouse Ym1 by sequence identity (Fig. 1). Overall, next to similarities, murine and human alternatively activated myeloid cells exhibit distinct differences. These should be taken into consideration to make optimal use of information obtained from murine models, and to relate it to the human situation.
References
Scotton, C. J., F. O. Martinez, M. J. Smelt, M. Sironi, M. Locati, A. Mantovani, S. Sozzani. 2005. Transcriptional profiling reveals complex regulation of the monocyte IL-1 system by IL-13. J. Immunol. 174: 834-845.
Welch, J. S., L. Escoubet-Lozach, D. B. Sykes, K. Liddiard, D. R. Greaves, C. K. Glass. 2002. TH2 cytokines and allergic challenge induce Ym1 expression in macrophages by a STAT6-dependent mechanism. J. Biol. Chem. 277: 42821-42829.
Loke, P., M. G. Nair, J. Parkinson, D. Guiliano, M. Blaxter, J. E. Allen. 2002. IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype. BMC Immunol. 3: 7.
Mohrs, M., B. Ledermann, G. K?hler, A. Dorfmüller, A. Gessner, F. Brombacher. 1999. Differences between IL-4- and IL-4 receptor -deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling. J. Immunol. 162: 7302-7308.
McKenzie, G. J., P. G. Fallon, C. L. Emson, R. K. Grencis, A. N. McKenzie. 1999. Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses. J. Exp. Med. 189: 1565-1573.
Hart, P. H., C. S. Bonder, J. Balogh, H. L. Dickensheets, R. P. Donnelly, J. J. Finlay-Jones. 1999. Differential responses of human monocytes and macrophages to IL-4 and IL-13. J. Leukocyte Biol. 66: 575-578.(Geert Raes, Rafa?l Van de)
References
Scotton, C. J., F. O. Martinez, M. J. Smelt, M. Sironi, M. Locati, A. Mantovani, S. Sozzani. 2005. Transcriptional profiling reveals complex regulation of the monocyte IL-1 system by IL-13. J. Immunol. 174: 834-845.
Welch, J. S., L. Escoubet-Lozach, D. B. Sykes, K. Liddiard, D. R. Greaves, C. K. Glass. 2002. TH2 cytokines and allergic challenge induce Ym1 expression in macrophages by a STAT6-dependent mechanism. J. Biol. Chem. 277: 42821-42829.
Loke, P., M. G. Nair, J. Parkinson, D. Guiliano, M. Blaxter, J. E. Allen. 2002. IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype. BMC Immunol. 3: 7.
Mohrs, M., B. Ledermann, G. K?hler, A. Dorfmüller, A. Gessner, F. Brombacher. 1999. Differences between IL-4- and IL-4 receptor -deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling. J. Immunol. 162: 7302-7308.
McKenzie, G. J., P. G. Fallon, C. L. Emson, R. K. Grencis, A. N. McKenzie. 1999. Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses. J. Exp. Med. 189: 1565-1573.
Hart, P. H., C. S. Bonder, J. Balogh, H. L. Dickensheets, R. P. Donnelly, J. J. Finlay-Jones. 1999. Differential responses of human monocytes and macrophages to IL-4 and IL-13. J. Leukocyte Biol. 66: 575-578.(Geert Raes, Rafa?l Van de)