Our laboratory uses a murine model of lymphatic filariasis that involves the peritoneal implant of the filarial nematode<i> Brugia malayi</i> to obtain a source of macrophages activated <i>in vivo</i> in chronic Th2 inflammatory conditions. These ‘nematode-elicited’ macrophages (NeMф) show a highly IL-4 dependent phenotype including the ability to suppress the proliferation of a wide range of cells and the expression of Arginase1, a characteristic marker of alternative activation. We decided to take a genomic approach to define what genes determine the IL-4 dependent phenotype of NeMф. This analysis revealed the striking expression of Fizz1 and Ym1; genes of uncertain function. We have shown that Fizzl and Ym1 expression is a characteristic feature of nematode infection and that expression is induced at the site of parasite migration or residence. Both genes are also directly responsive to IL-4 and IL-13, and are therefore reliable markers of Th2-driven immune responses. Finally, the study of their expression profile in haematopoietic cells showed restriction to antigen presenting cells, pointing to a role in shaping the immune response by regulating antigen presentation. Having originally characterised NeMф in C57BL/6 mice, we wanted to see whether the NeMф function was similar in BALB/c mice, the other commonly used mouse strain in our laboratory. In BALB/c mice, we found that both the function and gene expression of NeMф was not IL-4 dependent, and showed that this was due to compensation by the Th2 cytokine IL-13. The dependence on Th2 cytokines and the high expression of Arginase1 and Ym1 suggests that NeMф may mediate wound repair; one of the hypothesized functions of alternatively activated macrophages.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:659856 |
| Date | January 2003 |
| Creators | Nair, Meera Goh |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/15479 |
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