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10:07
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
SR-A ligand and M-CSF dynamically regulate SR-A expression and function in primary macrophages via p38 MAPK
Dejan Nikolic1, Lindsay Calderon, Liqin Du
1Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
BMC Immunology
|July 9, 2011
Summary
Inflammation dynamically alters macrophage scavenger receptor A (SR-A) expression. Ligand binding to SR-A up-regulates its expression and activates p38 MAPK, influencing inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Inflammation involves dynamic changes in cytokines like M-CSF and lipid/protein modifications, forming ligands for Class A Scavenger Receptors (SR-A).
- Altered SR-A expression in macrophages during inflammation is observed, but intracellular signaling pathways and ligand-mediated regulation remain unclear.
Purpose of the Study:
- To investigate the intracellular signal pathways regulating SR-A expression in macrophages.
- To determine how SR-A ligands modulate SR-A expression in resident mouse peritoneal macrophages.
Main Methods:
- Resident mouse peritoneal macrophages were incubated with M-CSF or acetylated-LDL (AcLDL), a selective SR-A ligand.
- SR-A expression, function, and p38 MAPK, ERK1/2, and JNK activation were assessed.
Main Results:
- M-CSF increased SR-A expression and function, dependent on p38 MAPK activation.
- SR-A expression returned to basal levels after M-CSF removal.
- Unlike most receptors, SR-A expression was reversibly increased by AcLDL, requiring p38 activation in wild-type but not SR-A-/- macrophages.
Conclusions:
- SR-A expression and function are dynamically regulated by inflammatory microenvironments in macrophages.
- Ligand binding to SR-A plays a previously unrecognized role in up-regulating SR-A expression and activating p38 MAPK.
- SR-A may modulate inflammatory responses by enhancing macrophage uptake and regulating cytokine production.
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