Mouse macrophage development in the absence of the common gamma chain: defining receptor complexes responsible for IL-4 and IL-13 signaling.
The common gamma chain (gamma c) forms a critical component of the receptors for interleukins (IL)-2, IL-4, IL-7, IL-9, and IL-15. We analyzed gamma c-deficient mice to define a role for gamma c signaling in the development and function of the macrophage lineage. No major differences in absolute cell numbers, cell surface phenotype, or in vitro function of gamma c- compared to gamma c+ macrophages were observed. We therefore conclude that signaling through the gamma c chain is not essential for the differentiation of mouse macrophages. Although B and T cells require gamma c for IL-4 responses, IL-4 up-regulated major histocompatibility class II molecules and inhibited nitric oxide production from gamma c- macrophages following stimulation with lipopolysaccharide and interferon-gamma. gamma c- macrophages could also respond to IL-13, consistent with the model of a type II IL-4 receptor alpha/IL-13R which can function in the absence of gamma c. Both IL-4 and IL-13 responses could be completely inhibited with the mouse IL-4 antagonist OY, suggesting that all of the observed IL-13 responses pass through the type II receptor, making it the primary signaling receptor complex for IL-13 in mouse macrophages.
Andersson
A
A
INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
Grunewald
S M
SM
Duschl
A
A
Fischer
A
A
DiSanto
J P
JP
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D016130:Immunophenotyping; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
D018793:Interleukin-13; D018123:Receptors, Interleukin; D015847:Interleukin-4; D009569:Nitric Oxide