Expression of the chemokine N51/KC in the thymus and epidermis of transgenic mice results in marked infiltration of a single class of inflammatory cells.
Open accessAbstract
Transgenic mice expressing the chemokine N51/KC in thymus, skin, and tongue showed a marked infiltration of a single class of inflammatory cells (neutrophils) in the sites of transgene expression. In the thymus, neutrophils were most numerous in the cortex and juxta-medullary regions, often forming aggregates or clusters. A similar, but less intense, neutrophilic infiltrate occurred in close proximity to the epidermal basal layer of the tongue and skin. No morphologic evidence of injury was observed in the thymus, skin, or tongue of these transgenic mice, indicating that N51/KC expression induces recruitment but not inflammatory activation of neutrophils. The lack of activation in the thymus resulted in a large senescent neutrophilic population that was phagocytosed by thymic macrophages and epithelial-reticular cells. These results indicate that N51/KC is a neutrophil chemoattractant in vivo and establish these transgenic mice as effective models to study the phenomena of recruitment and clearance of neutrophils, events that are critical for the initiation and resolution of the inflammatory response.
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High systemic KC levels lead to impaired PMN activation via desensitization of the PMN CXC-receptor 2.
“However, KC alone is not sufficient for the activation of infiltrated cells, and high systemic KC levels lead to impaired PMN activation via desensitization of the PMN CXC-receptor 2 (46).”
From The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell–mediated liver injury (2005) · cites this paper as [46]
The Discussion (p. 2046) says chronic N51/KC expression recruits neutrophils without inflammatory activation and suggests that activation such as degranulation requires other mediators. It does not report that high systemic KC impairs PMN activation or that CXC-receptor 2 desensitization causes such impairment. (LLM, conf=0.88)
Experimental — accuracy not yet measuredKC alone is not sufficient for the activation of infiltrated cells.
“However, KC alone is not sufficient for the activation of infiltrated cells, and high systemic KC levels lead to impaired PMN activation via desensitization of the PMN CXC-receptor 2 (46).”
From The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell–mediated liver injury (2005) · cites this paper as [46]
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Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909 · see citing works
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Delayed Wound Healing and Epidermal Hyperproliferation in Mice Lacking JunB in the Skin
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Transient Lung-Specific Expression of the Chemokine KC Improves Outcome in Invasive Aspergillosis
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Self-citationNeutrophils Regulate Airway Responses in a Model of Fungal Allergic Airways Disease
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- Authors
- Lira, S. A., Zalamea, P., Heinrich, J. N., Fuentes, M. E., Carrasco, D., Lewin, A. C., Barton, D. S., Durham, S., & Bravo, R.
- Affiliations
- Bristol-Myers Squibb (United States) (US)
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1994-12-01
- Volume
- 180
- Issue
- 6
- Pages
- 2039-2048
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2191760
- OpenAlex
- W2058498759
- Cited by
- 115
- References
- 1
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 8
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- University of Washington
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- neutrophil recruitment, neutrophil chemoattractants, transgenic mice, thymus, epidermis, tongue, neutrophil aggregation, neutrophil clearance, thymic macrophages, chemokine expression
- MeSH terms
- Aging, Animals, Base Sequence, Chemotactic Factors, Growth Substances, Humans, Inflammation, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Microscopy, Electron, Molecular Sequence Data, Neutrophils, Oligodeoxyribonucleotides, Skin, Growth Hormone, Thymus Gland, Tongue, Gene Expression, Chemokines, CXC, Intercellular Signaling Peptides and Proteins, Mice, Chemokine CXCL1
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