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Updated: Jul 14, 2026
Isolation and Culture of Primary Synovial Macrophages and Fibroblasts from Murine Arthritis Tissue
Published on: February 24, 2023
Mechanisms of disease: a 'DAMP' view of inflammatory arthritis
Dirk Foell1, Helmut Wittkowski, Johannes Roth
1Department of Pediatrics, University of Muenster, Muenster, Germany. dfoell@uni-muenster.de
Abstract:
Innate immunity achieves our primary host defense by recognizing invading microorganisms through pathogen-associated molecular patterns (PAMPs) and by reacting to tissue damage signals called damage-associated molecular patterns (DAMPs). DAMP molecules, including high mobility group box 1 protein (HMGB-1), heat-shock proteins (HSPs), uric acid, altered matrix proteins, and S100 proteins, represent important danger signals that mediate inflammatory responses through the receptor for advanced glycation end-products (RAGE, also known as AGER) and Toll-like receptors, after release from activated or necrotic cells. The terms 'alarmins' and 'endokines' have also been proposed for DAMP molecules. A prototypic DAMP molecule, the nuclear protein HMGB-1, is either passively released by necrotic cells or actively secreted with delay by activated cells. S100A8, S100A9, and S100A12 are calcium-binding proteins expressed in the cytoplasm of phagocytes. They are rapidly secreted by activated monocytes or neutrophils, which are abundant in inflamed synovial tissue. HSPs are involved in the crosstalk between innate and adaptive immune systems, and primarily mediate immune regulatory functions. Multiple positive feedback loops between DAMPs and PAMPs and their overlapping receptors temporally and spatially drive these processes and may represent the molecular basis for the observation that infections, as well as nonspecific stress factors, can trigger flares in rheumatic diseases.
Insights
Damage-associated molecular patterns (DAMPs) are danger signals that activate innate immunity. These molecules, like HMGB-1 and HSPs, mediate inflammatory responses and may link infections to flares in rheumatic diseases.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Biology
Background:
- Innate immunity provides host defense by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).
- DAMPs are released from damaged or activated cells and act as danger signals, initiating inflammatory responses.
- Examples of DAMPs include HMGB-1, HSPs, uric acid, and S100 proteins, which signal through receptors like RAGE and Toll-like receptors.
Purpose of the Study:
- To elucidate the role of DAMPs in innate immunity and inflammation.
- To explore the mechanisms by which DAMPs mediate inflammatory responses.
- To investigate the potential link between DAMPs, infections, and rheumatic disease flares.
Main Methods:
- The abstract does not specify methods, but discusses molecular mechanisms of DAMPs.
- Focuses on the release and signaling pathways of DAMP molecules.
- Highlights the involvement of specific DAMPs like HMGB-1 and S100 proteins in immune cell activation.
Main Results:
- DAMP molecules are crucial mediators of inflammatory responses.
- HMGB-1 is released by necrotic cells or secreted by activated cells.
- S100 proteins are rapidly secreted by activated phagocytes and are abundant in inflamed tissues.
- HSPs play a role in immune regulation and crosstalk between innate and adaptive immunity.
Conclusions:
- DAMPs are essential components of the innate immune system's response to cellular damage and stress.
- Positive feedback loops between DAMPs and PAMPs contribute to sustained inflammation.
- DAMP signaling pathways may underlie the exacerbation of rheumatic diseases by infections or stress.
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