%0 Journal Article
%T IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype
%A P'ng Loke
%A Meera G Nair
%A John Parkinson
%A David Guiliano
%A Mark Blaxter
%A Judith E Allen
%J BMC Immunology
%D 2002
%I BioMed Central
%R 10.1186/1471-2172-3-7
%X We have used murine macrophages elicited by nematode infection (NeM¦Õ) as a source of in vivo derived alternatively activated macrophages. Using three distinct yet complementary molecular approaches we have established a gene expression profile of alternatively activated macrophages and identified macrophage genes that are regulated in vivo by IL-4. First, genes abundantly expressed were identified by an expressed sequence tag strategy. Second, an array of 1176 known mouse genes was screened for differential expression between NeM¦Õ from wild type or IL-4 deficient mice. Third, a subtractive library was screened to identify novel IL-4 dependent macrophage genes. Differential expression was confirmed by real time RT-PCR analysis.Our data demonstrate that alternatively activated macrophages generated in vivo have a gene expression profile distinct from any macrophage population described to date. Several of the genes we identified, including those most abundantly expressed, have not previously been associated with macrophages and thus this study provides unique new information regarding the phenotype of macrophages found in Th2-mediated, chronic inflammatory settings. Our data also provide additional in vivo evidence for parallels between the inflammatory processes involved in nematode infection and allergy.Macrophages play a crucial role in innate as well as adaptive immune responses to pathogens, and are thought to be critical mediators of many chronic inflammatory diseases [1-4]. During inflammation, the signals that monocytes encounter during migration to the inflammatory site direct their maturation into macrophages with distinct phenotypes. The best-studied macrophage phenotype is the classically-activated macrophage which develops in response to pro-inflammatory stimuli such as Th1 cytokines or bacterial products. Activation of macrophages by bacterial products such as LPS and CpG DNA often occurs as a result of engaging receptors of the Toll family [5], leading
%U http://www.biomedcentral.com/1471-2172/3/7