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Updated: May 30, 2025
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Imaging CD4 T Cell Interstitial Migration in the Inflamed Dermis
Published on: March 25, 2016
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Large soluble CD18 complexes with exclusive ICAM-1-binding properties are shed during immune cell migration in
Alexey Ferapontov1, Anders Mellemkjær1, Helen M McGettrick2
1Department of Biomedicine, Aarhus University, Denmark.
Journal of Translational Autoimmunity
|January 27, 2025
Summary
Soluble CD18 (sCD18) complexes regulate inflammation by influencing cytokine release. Large sCD18 complexes bind to ICAM-1 and are shed by neutrophils, explaining their prevalence in rheumatoid arthritis (RA) inflammation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- CD11/CD18 integrins are crucial for leukocyte adhesion and migration in physiological and pathological inflammatory responses.
- Soluble CD18 (sCD18) exists in different complex sizes, potentially indicating functional variations.
- Previous studies showed sCD18 complexes can bind intercellular adhesion molecule (ICAM)-1, but functional differences related to size remained unclear.
Purpose of the Study:
- To investigate the functional significance of sCD18 complex size in regulating inflammation.
- To determine the role of sCD18 complexes in cytokine release and ICAM-1 binding.
- To correlate sCD18 complex characteristics with inflammatory processes in rheumatoid arthritis (RA).
Main Methods:
- Analysis of sCD18 complex sizes and their association with ICAM-1 binding.
- Assessment of sCD18's effect on monocyte chemoattractant protein-1 (MCP-1/CCL2) release from fibroblast-like synovial cells.
- Characterization of sCD18 complexes shed by migrating neutrophils.
- Comparison of sCD18 complex profiles in patients with RA.
Main Results:
- Serum sCD18 regulates the release of the proinflammatory cytokine MCP-1/CCL2.
- Only large sCD18 complexes exhibit ICAM-1 binding capability.
- Migrating neutrophils predominantly shed large sCD18 complexes.
- Large sCD18 complexes are prevalent in RA inflammatory sites, correlating with neutrophil influx.
Conclusions:
- sCD18 complex size is a critical determinant of its function in regulating inflammation.
- Large sCD18 complexes play a significant role in inflammatory processes by binding ICAM-1 and mediating cytokine release.
- These findings elucidate a novel mechanism of inflammation regulation by sCD18 and suggest potential therapeutic targets for inflammatory diseases like arthritis.
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