Increased macrophage colony-stimulating factor in neonatal and adult autoimmune MRL-lpr mice.
Abnormal macrophages in MRL-lpr mice are implicated in the pathogenesis of autoimmune disease. These mice die of lupus nephritis by 5 to 6 months of age. This study reports that MRL-lpr mice have an increased level of circulating macrophage colony-stimulating factor (M-CSF) detectable as early as 1 week of age. Macrophage colony-stimulating factor decreased between 2 and 4 months and then steadily increased beginning at 4 months of age. In contrast, M-CSF was not detected in sera from congenic MRL-++ mice, normal C3H/FeJ mice, two other mouse strains with the lpr gene (B6-lpr and C3H-lpr), or another lupus model, the NZB/W mouse. These observations indicate that the lpr gene alone is not responsible for inducing this growth factor, and elevated M-CSF is not required for all forms of murine lupus. The entire source of serum M-CSF is not clear. The unique T cells regulated by the lpr gene are not responsible for the increased serum M-CSF levels, as no M-CSFs could be detected in supernatants from cultured lymph nodes from MRL-lpr mice, and the steady-state levels of M-CSF mRNA in lymph nodes and spleens in MRL-lpr, C3H-lpr mice and in their respective congenic strains were similar. The steady-state M-CSF mRNA transcripts in liver, lung, and bone marrow in MRL-lpr, MRL-++, and C3H/FeJ mice were also similar. Macrophage colony-stimulating factor transcripts were clearly elevated in the kidneys of MRL-lpr mice, suggesting a renal source of circulating M-CSF. The increase of M-CSF might be responsible for the increased numbers and enhanced functions of macrophages, which in turn cause tissue destruction in MRL-lpr mice.
Yui
M A
MA
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, Massachusetts.
Brissette
W H
WH
Brennan
D C
DC
Wuthrich
R P
RP
Rubin-Kelley
V E
VE
D000818:Animals; D000831:Animals, Newborn / Q000097:blood*; D015551:Autoimmunity; D005260:Female; D005796:Genes; D008177:Lupus Vulgaris / Q000235:genetics / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains / Q000097:blood* / Q000235:genetics / Q000276:immunology; D012727:Sex Characteristics; D014018:Tissue Distribution
D016173:Macrophage Colony-Stimulating Factor