Direct evidence for an intracellular role for IFN-gamma. Microinjection of human IFN-gamma induces Ia expression on murine macrophages.
An intracellular action for IFN-gamma was detected by using microinjection technology. Human IFN-gamma (huIFN-gamma) does not ordinarily act on murine cells because it fails to bind to murine cell surface receptors. However, when huIFN-gamma was microinjected into murine macrophages, a time and dose-dependent induction of Ia was detected by autoradiography on the surface of injected and neighboring cells. These results imply a direct role for internalized IFN-gamma and show that huIFN-gamma, although it fails to be recognized by murine cell surface receptors, can act internally on murine cells. The effect on Ia gene expression induced by microinjected huIFN-gamma was in part indirect: granulocyte/macrophage-CSF (GM-CSF) was released by IFN-gamma-injected macrophages, and this secondary mediator appeared to induce Ia on neighboring cells, inasmuch as anti-GM-CSF blocked Ia induction. Anti-GM-CSF also partially blocked Ia induction by extracellular murine IFN-gamma on murine macrophages. Thus, at least some of the Ia induction attributed to IFN-gamma was mediated by GM-CSF.
Smith
M R
MR
Program Resources, Inc., National Cancer Institute-Frederick Cancer Research Facility, MD 21701.
Muegge
K
K
Keller
J R
JR
Kung
H F
HF
Young
H A
HA
Durum
S K
SK
D000818:Animals; D001345:Autoradiography; D003115:Colony-Stimulating Factors / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007158:Immunologic Techniques; D007371:Interferon-gamma / Q000008:administration & dosage / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008845:Microinjections; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor