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Published August 1991 | public
Journal Article

Increased macrophage colony-stimulating factor in neonatal and adult autoimmune MRL-lpr mice

Abstract

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.

Additional Information

© American Association of Pathologists. Accepted for publication March 12, 1991. The authors thank Drs. C. B. Carpenter and David L. Perkins for carefully reviewing this manuscript. Supported by NIH grants DK-36149, DK-40839, and CA-48626 (to Vicki Rubin-Kelley), Al-07918 (to Daniel Brennan), and a grant from the Jules and Gwen Knapp Chartable Foundation. Rudolph Wuthrich is a recipient of a grant from the Swiss National Science Foundation.

Additional details

Created:
August 20, 2023
Modified:
October 24, 2023