Macrophage colony stimulating factor increases hepatic macrophage content, liver growth and lipid accumulation in neonatal rats.

Clare Pridans, Kristin Sauter, K. Irvine, Lucas Lefevre, Anna Raper, Rocío Rojo, Ajit johnson Nirmal, Philippa Beard, Michael Cheeseman, David Hume

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Signaling via the colony stimulating factor 1 receptor (CSF1R) controls the survival, differentiation and proliferation of macrophages. Mutations in CSF1, or CSF1R in mice and rats have pleiotropic effects on postnatal somatic growth. We tested the possible application of CSF1-Fc as a therapy for low birth weight (LBW) at term, using a model based upon maternal dexamethasone treatment in rats. Neonatal CSF1-Fc treatment did not alter somatic growth, and did not increase the blood monocyte count. Instead, there was a substantial increase in the size of liver in both control and LBW rats, and the treatment greatly exacerbated the lipid droplet accumulation seen in the dexamethasone LBW model. These effects were reversed upon cessation of treatment. Transcriptional profiling of the livers supported histochemical evidence of a large increase in macrophages with a resident Kupffer cell phenotype, and revealed increased expression of many genes implicated in lipid droplet formation. There was no further increase in hepatocyte proliferation over the already high rates in neonatal liver.
Conclusion: Treatment of neonatal rats with CSF1-Fc caused an increase in liver size and hepatic lipid accumulation, due to Kupffer cell expansion and/or activation rather than hepatocyte proliferation. Increased liver macrophage numbers and expression of endocytic receptors could mitigate defective clearance functions in neonates
Original languageEnglish
Pages (from-to)G388-G398
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume314
Issue number3
Early online date21 Dec 2017
DOIs
Publication statusPublished - Mar 2018

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