The chemokine receptor CXCR2 ligand KC (CXCL1) mediates neutrophil recruitment and is critical for development of experimental lyme arthritis and carditis
Open accessAbstract
Deletion of the chemokine receptor CXCR2 prevents the recruitment of neutrophils into tissues and subsequent development of experimental Lyme arthritis. Following footpad inoculation of Borrelia burgdorferi, the agent of Lyme disease, expression of the CXCR2 ligand KC (CXCL1) is highly upregulated in the joints of arthritis-susceptible mice and is likely to play an important role in the recruitment of neutrophils to the site of infection. To test this hypothesis, we infected C3H KC−/−mice with B. burgdorferi and followed the development of arthritis and carditis. Ankle swelling was significantly attenuated during the peak of arthritis in the KC−/−mice. Arthritis severity scores were significantly lower in the KC−/−mice on days 11 and 21 postinfection, with fewer neutrophils present in the inflammatory lesions. Cardiac lesions were also significantly decreased in KC−/−mice at day 21 postinfection. There were, however, no differences between C3H wild-type and KC−/−mice in spirochete clearance from tissues. Two other CXCR2 ligands, LIX (CXCL5) and MIP-2 (CXCL2), were not increased to compensate for the loss of KC, and the production of several innate cytokines was unaltered. These results demonstrate that KC plays a critical nonredundant role in the development of experimental Lyme arthritis and carditis via CXCR2-mediated recruitment of neutrophils into the site of infection.
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LIX/ENA-78 levels are present at normal levels in THS-exposed mouse wounds.
“Although the levels of KC, chemoattractant for neutrophils [57,58], were reduced in the THS-exposed mouse wounds the levels of LIX/ENA-78, another chemokine that chemoattracts neutrophils was present at normal levels [59].”
From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [58]
The Discussion identifies LIX as a chemokine that mediates neutrophil recruitment, and the Results report unchanged LIX levels in infected ankles and hearts of KC-deficient mice. The paper does not study THS-exposed wounds, so it does not establish that LIX/ENA-78 levels were normal in those wounds. (LLM, conf=0.88)
Experimental — accuracy not yet measuredKC levels are reduced in THS-exposed mouse wounds.
“Although the levels of KC, chemoattractant for neutrophils [57,58], were reduced in the THS-exposed mouse wounds the levels of LIX/ENA-78, another chemokine that chemoattracts neutrophils was present at normal levels [59].”
From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [58]
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- Authors
- Ritzman, A. M., Hughes-Hanks, J. M., Blaho, V. A., Wax, L. E., Mitchell, W. J., & Brown, C. R.
- Affiliations
- University of Missouri (US)
- Corresponding author
- Brown, Charles R.
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2010-11
- Volume
- 78
- Issue
- 11
- Pages
- 4593-4600
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC2976349
- OpenAlex
- W2108854943
- Cited by
- 123
- References
- 0
- Citations by year
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- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI059292, AI059292)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR052748, AR052748)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- CXCL1, KC chemokine, CXCR2, neutrophil recruitment, Lyme arthritis, Lyme carditis, Borrelia burgdorferi, CXCL5, CXCL2, innate cytokines, joint inflammation
- MeSH terms
- Animals, Arthritis, Experimental, Disease Models, Animal, Female, Ligands, Lyme Disease, Male, Mice, Inbred C3H, Myocarditis, Neutrophils, Severity of Illness Index, Signal Transduction, Mice, Knockout, Neutrophil Infiltration, Receptors, Interleukin-8B, Borrelia burgdorferi, Mice, Chemokine CXCL1
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