M-CSF transgenic mice: role of M-CSF in infection and autoimmunity.
In this study, transgenic CD2F1 mouse lines (C-1.1-C-1.11) bearing a transgene encoding the murine growth factor M-CSF under the control of the liver specific alpha-1-antitrypsin gene promoter were generated. Transgenic C-1.4 mice showed elevated expression of transgene-encoded M-CSF in the liver and displayed a 2-3-fold increase of M-CSF plasma levels and of macrophage numbers in the liver as compared with non-transgenic littermates. M-CSF transgenic mice showed increased resistance against sublethal i.v. infections with Listeria monocytogenes as compared with infected non-transgenic mice. To investigate the influence of M-CSF in murine systemic lupus erythematosus (SLE), the M-CSF transgenic mouse line C-1.4 was bred into the genetic background of SLE-prone MRL+/+ mice. The resulting C-1.4/MRL transgenic mice bearing increased endogenous M-CSF levels showed consistently lower levels of anti-ss-DNA autoantibodies as compared with non-transgenic MRL+/+ mice. The life span of the C- 1.4/MRL transgenic mice and the severity of the disease in these mice remained unchanged as compared with their non-transgenic littermates. It is concluded that in addition to M-CSF further factors must be involved in the acceleration of the autoimmune disease in SLE prone MRL/lpr mice.
Bernier
T
T
Fraunhofer Institute of Toxicology and Aerosol Research, Department of Immunobiology, Hannover, Germany.
Halter
R
R
Pau
D
D
Rittinghausen
S
S
Emmendörffer
A
A
D000818:Animals; D000974:Antibodies, Antinuclear; D015139:Blotting, Southern; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D018703:Founder Effect; D008017:Life Expectancy; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008136:Longevity; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood / Q000235:genetics*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism
D000974:Antibodies, Antinuclear; D016207:Cytokines; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor