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Updated: Aug 11, 2026
Bone Marrow-derived Macrophage Production
Published on: November 22, 2013
The macrophage scavenger receptor type A is expressed by activated macrophages and protects the host against lethal
1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Abstract:
During gram-negative bacterial infections, lipopolysaccharide (LPS) stimulates primed macrophages (Mphi) to release inflammatory mediators such as tumor necrosis factor (TNF)-alpha, which can cause hypotension, organ failure, and often death. Several different receptors on Mphi have been shown to bind LPS, including the type A scavenger receptor (SR-A). This receptor is able to bind a broad range of polyanionic ligands such as modified lipoproteins and lipoteichoic acid of gram-positive bacteria, which suggests that SR-A plays a role in host defense. In this study, we used mice lacking the SR-A (SRKO) to investigate the role of SR-A in acquired immunity using a viable bacillus Calmette Guérin (BCG) infection model. We show that activated Mphi express SR-A and that this molecule is functional in assays of adhesion and endocytic uptake. After BCG infection, SRKO mice are able to recruit Mphi to sites of granuloma formation where they become activated and restrict BCG replication. However, infected mice lacking the SR-A are more susceptible to endotoxic shock and produce more TNF-alpha and interleukin-6 in response to LPS. In addition, we show that an antibody which blocks TNF-alpha activity reduces LPS-induced mortality in these mice. Thus SR-A, expressed by activated Mphi, plays a protective role in host defense by scavenging LPS as well as by reducing the release by activated Mphi of proinflammatory cytokines. Modulation of SR-A may provide a novel therapeutic approach to control endotoxic shock.
Insights
The scavenger receptor A (SR-A) protects against endotoxic shock by binding lipopolysaccharide (LPS). Mice lacking SR-A show increased susceptibility to LPS, highlighting SR-A
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Lipopolysaccharide (LPS) from gram-negative bacteria triggers inflammatory responses in macrophages (Mphi).
- The scavenger receptor A (SR-A) on Mphi binds LPS and other anionic molecules, suggesting a role in host defense.
- The function of SR-A in acquired immunity and response to bacterial infections remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of SR-A in acquired immunity using a mouse model of Bacillus Calmette-Guérin (BCG) infection.
- To determine SR-A's contribution to host defense against LPS-induced endotoxic shock.
Main Methods:
- Utilized SR-A knockout (SRKO) mice and a viable BCG infection model.
- Assessed Mphi recruitment, activation, and BCG replication at granuloma sites.
- Measured TNF-alpha and IL-6 production in response to LPS.
- Evaluated the effect of TNF-alpha blockade on LPS-induced mortality.
Main Results:
- Activated Mphi express functional SR-A involved in adhesion and endocytosis.
- SRKO mice successfully recruited and activated Mphi for BCG control but were more susceptible to endotoxic shock.
- SRKO mice exhibited elevated TNF-alpha and IL-6 production upon LPS challenge.
- Antibody-mediated blockade of TNF-alpha reduced LPS-induced mortality in SRKO mice.
Conclusions:
- SR-A expressed by activated Mphi plays a crucial protective role in host defense.
- SR-A functions by scavenging LPS and mitigating the release of pro-inflammatory cytokines.
- Targeting SR-A presents a potential therapeutic strategy for managing endotoxic shock.
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