IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype.
BACKGROUND
"Alternatively-activated" macrophages are found in Th2-mediated inflammatory settings such as nematode infection and allergic pulmonary inflammation. Due in part to a lack of markers, these cells have not been well characterized in vivo and their function remains unknown.


RESULTS
We have used murine macrophages elicited by nematode infection (NeM(phi)) 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(phi) 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.


CONCLUSIONS
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.
Loke
P'ng
P
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, UK. ploke@uclink.berkeley.edu
Nair
Meera G
MG
Parkinson
John
J
Guiliano
David
D
Blaxter
Mark
M
Allen
Judith E
JE
D000818:Animals; D001119:Arginase / Q000235:genetics; D017178:Brugia malayi / Q000254:growth & development / Q000276:immunology; D020224:Expressed Sequence Tags; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D015723:Gene Library; D005838:Genotype; D036341:Intercellular Signaling Peptides and Proteins; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015848:Interleukin-5 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020932:Nerve Growth Factor; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics
D036341:Intercellular Signaling Peptides and Proteins; D015848:Interleukin-5; D011506:Proteins; C413576:Retnla protein, mouse; D015847:Interleukin-4; D020932:Nerve Growth Factor; D001119:Arginase