Recently, Raes et al. (1) responded in a letter to the editor to a paper of Scotton et al. (2) dealing with the effects of IL-13 on the transcriptional profile of human monocytes and those of IL-4 on murine macrophages (3, 4). The discussion dealt with the differences that were observed in these separate studies with regard to the expression of YM1 and arginase I, which are both up-regulated in mouse macrophages but not in human monocytes (1). The point that Raes et al. make is that the differences observed could also be ascribed to differences between human and mouse macrophages rather than differences in the effects of IL-4 and IL-13 as proposed by Scotton et al.
To support their proposal, Raes et al. show that IL-4 combined with IL-13 does not induce arginase-1 or eosinophil chemotactic cytokine (CHIA) in human macrophages contrasting to the situation in mouse cells, indicating that murine and human alternatively activated myeloid cells exhibit differences (1).
We would like to point out that human CHIA is not the orthologue of mouse YM1. CHIA is an alternative name for human acidic mammalian chitinase (AMCase). It erroneously received this name due to its sequence identity to YM1, also known as eosinophil chemotactic factor, the closest homologue at that time. More recently we demonstrated that the true orthologue of human AMCase is mouse AMCase (both active chitinases) and not YM1 (5). Moreover close examination of the mouse and human genome suggests that there is no human orthologue of YM1. It seems that the mammalian members of the chitinase family have arisen from several separate duplication events in these different species.
Therefore we feel that the comparison between mouse YM1 and human AMCase is not valid as an argument for the alternative explanation of Raes et al. However, it is interesting to note that Zhu et al. recently described that an IL-13-dependent mechanism was responsible for the induced AMCase expression in alveolar macrophages and lung epithelial cells in a mouse aeroallergen asthma model (6). Since Raes et al. did not observe any induction of AMCase by IL-4/IL-13 in human macrophages, this seems to support their hypothesis that important differences exist between human and mouse alternatively activated macrophages.
