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Updated: Aug 12, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Lipopolysaccharide induces scavenger receptor A expression in mouse macrophages: a divergent response relative to
M L Fitzgerald1, K J Moore, M W Freeman
1Harvard School of Public Health and Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Gene deletion studies indicate that the macrophage scavenger receptor A (SR-A) protects mice from LPS-induced endotoxemia. Paradoxically, cultured human monocyte-derived macrophages down-regulate SR-A expression when exposed to LPS. We found that human THP-1 monocyte/macrophages decrease SR-A expression in response to LPS independent of their differentiation status. In contrast, primary and elicited mouse peritoneal macrophages as well as the J774A.1 and RAW264.7 mouse macrophage lines increase SR-A expression in response to LPS. Exposure to LPS caused J774A.1 and RAW264.7 cells to increase SR-A transcripts by 3- and 5-fold, respectively. LPS caused a concomitant 3-fold increase in SR-A protein levels and increased cell membrane expression of the receptor. RAW264.7 cells increased SR-A transcript levels in response to LPS at concentrations as low as 1 ng/ml, and the response was saturated at 10 ng/ml. The LPS induction of SR-A transcripts required continual protein synthesis and began at 8 h, peaked by 16 h, and persisted for at least 48 h. LPS induction did not increase SR-A gene transcription or affect alternative transcript splicing, but mildly increased mature transcript stability and proceeded in the presence of actinomycin D. Finally, treatment of RAW264.7 cells with TNF-alpha did not induce SR-A transcript levels, indicating that a TNF-alpha autocrine/paracrine signaling mechanism alone is not sufficient to recapitulate the LPS induction of SR-A transcripts. The induction of SR-A expression by LPS-stimulated mouse macrophages is the opposite of the down-regulation of SR-A reported in human monocyte-derived macrophages and may have implications for the observed resistance mice show toward endotoxemia.
Insights
Macrophage scavenger receptor A (SR-A) expression differs between species upon LPS exposure. Mouse macrophages up-regulate SR-A, enhancing endotoxemia protection, while human macrophages down-regulate it.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Macrophage scavenger receptor A (SR-A) plays a role in protecting mice from lipopolysaccharide (LPS)-induced endotoxemia.
- Cultured human monocyte-derived macrophages paradoxically down-regulate SR-A expression when exposed to LPS.
Purpose of the Study:
- To investigate the differential regulation of SR-A expression by LPS in human and mouse macrophages.
- To elucidate the molecular mechanisms underlying LPS-induced SR-A modulation in macrophages.
Main Methods:
- Comparing SR-A expression (mRNA and protein) in human THP-1 cells and various mouse macrophage lines (primary peritoneal, elicited peritoneal, J774A.1, RAW264.7) after LPS stimulation.
- Analyzing SR-A gene transcription, transcript stability, and the role of protein synthesis and TNF-alpha signaling.
Main Results:
- Human THP-1 cells consistently decreased SR-A expression in response to LPS.
- Mouse macrophages (primary and cell lines) significantly increased SR-A transcript and protein levels following LPS exposure.
- LPS induction of SR-A in mouse cells involved increased transcript stability, required protein synthesis, and was not solely mediated by TNF-alpha.
Conclusions:
- LPS differentially regulates SR-A expression in human and mouse macrophages, with mouse macrophages up-regulating SR-A and human macrophages down-regulating it.
- This species-specific regulation of SR-A by LPS may contribute to the observed differences in endotoxemia resistance between mice and humans.
