Lymphocyte/macrophage interactions: biomaterial surface-dependent cytokine, chemokine, and matrix protein production
Open accessAbstract
The role of lymphocytes in the biological response to synthetic polymers is poorly understood despite the transient appearance of lymphocytes at the biomaterial implant site. To investigate cytokines, chemokines, and extracellular matrix (ECM) proteins produced by lymphocytes and macrophages in response to biomaterial surfaces, human peripheral blood monocytes and lymphocytes were co‐cultured on polyethylene terephthalate (PET)‐based material surfaces displaying distinct hydrophobic, hydrophilic/neutral, hydrophilic/anionic, and hydrophilic/cationic chemistries. Antibody array screening showed the majority of detected proteins are inflammatory mediators that guide the early inflammatory phases of wound healing. Proteomic ELISA quantification and adherent cell analysis were performed after 3, 7, and 10 days of culture. IL‐2 and IFN‐γ were not detected in any co‐cultures suggesting lack of lymphocyte activation. The hydrophilic/neutral surfaces increased IL‐8 relative to the hydrophobic PET surface ( p < 0.05). The hydrophilic/anionic surfaces promoted increased TNF‐α over hydrophobic and cationic surfaces and increased MIP‐1β compared to hydrophobic surfaces ( p < 0.05). Since enhanced macrophage fusion was observed on hydrophilic/anionic surfaces, the production of these cytokines likely plays an important role in the fusion process. The hydrophilic/cationic surface promoted IL‐10 production and increased matrix metalloproteinase (MMP)‐9/tissue inhibitor of MMP (TIMP) relative to hydrophilic/neutral and anionic surfaces ( p < 0.05). These results suggest hydrophilic/neutral and anionic surfaces promote pro‐inflammatory responses and reduced degradation of the ECM, whereas the hydrophilic/cationic surfaces induce an anti‐inflammatory response and greater MMP‐9/TIMP with an enhanced potential for ECM breakdown. The study also underscores the usefulness of protein arrays in assessing the role of soluble mediators in the inflammatory response to biomaterials. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
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Undetected lymphokines such as IL-2 and IFN-γ indicated the lack of classic T lymphocyte activation.
“Undetected lymphokines such as IL-2 and IFN-γ indicated the lack of classic T lymphocyte activation.”
From Foreign body reaction to biomaterials (2008) · cites this paper as [145]
Production of cytokines, chemokines, and extracellular matrix proteins were biomaterial surface chemistry dependent.
“However, the production of cytokines, chemokines, and extracellular matrix proteins were biomaterial surface chemistry dependent.[145]”
From Foreign body reaction to biomaterials (2008) · cites this paper as [145]
In an in vitro lymphocyte/macrophage co-culture study, juxtacrine and paracrine signaling play a crucial role in determining inflammatory response, and this response can be mediated by varying surface chemistry of materials.
“Indeed, it has been shown in an in vitro lymphocyte/macrophage co-culture study that juxtacrine (cell-cell contact) and paracrine (soluble factors) signaling play a crucial role in determining inflammatory response; and that this response can be mediated by varying surface chemistry of materials [71].”
From Biomaterial based modulation of macrophage polarization: a review and suggested design principles (2015) · cites this paper as [71]
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References 50 · Cited by 114
- Authors
- Chang, D. T., Jones, J. A., Meyerson, H., Colton, E., Kwon, I. K., Matsuda, T., & Anderson, J. M.
- Affiliations
- Case Western Reserve University (US)
- University Hospitals of Cleveland (US)
- Purdue University West Lafayette (US)
- Kyushu University (JP)
- Corresponding author
- Anderson, James M.
- Venue
- Journal of Biomedical Materials Research Part A
- Publisher
- Wiley
- Published
- 2008-01-15
- Volume
- 87A
- Issue
- 3
- Pages
- 676-687
- ISSN
- 1549-3296 (ISSN-L)
- 1552-4965
- PMC
- PMC3867010
- OpenAlex
- W2007697125
- Cited by
- 114
- References
- 50
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 3 · 2015: 9 · 2014: 6 · 2013: 2 · 2012: 4
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Biomedical Materials Research Part A (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM007250, T32GM07250)
- National Institute of Biomedical Imaging and Bioengineering (R37EB000275, #EB000282, EB 000275, R56EB000282, R01EB000282, R01EB000275)
- Topics
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- macrophage-lymphocyte interaction, cytokine production, chemokines, extracellular matrix proteins, polyethylene terephthalate, hydrophobic surfaces, macrophage fusion, TNF-α, interleukin-8, MIP-1β, IL-10, anti-inflammatory response, pro-inflammatory response, implant inflammation, wound healing
- MeSH terms
- Adult, Biocompatible Materials, Cells, Cultured, Humans, Lymphocyte Activation, Lymphocytes, Macrophages, Polyethylene Terephthalates, Cytokines, Extracellular Matrix Proteins, Coculture Techniques, Chemokines, Protein Array Analysis
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