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12/15-lipoxygenase regulates the inflammatory response to bacterial products in vivo

Dioszeghy, Vincent, Rosas, Marcela ORCID: https://orcid.org/0000-0002-9442-9638, Maskrey, Benjamin H., Colmont, Chantal Sophie, Topley, Nicholas, Chaitidis, Pavlos, Kühn, Hartmut, Jones, Simon Arnett ORCID: https://orcid.org/0000-0001-7297-9711, Taylor, Philip Russel ORCID: https://orcid.org/0000-0003-0163-1421 and O'Donnell, Valerie Bridget ORCID: https://orcid.org/0000-0003-4089-8460 2008. 12/15-lipoxygenase regulates the inflammatory response to bacterial products in vivo. The Journal of Immunology 181 (9) , pp. 6514-6524.

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Abstract

The peritoneal macrophage (Mφ) is the site of greatest 12/15-lipoxygenase (12/15-LOX) expression in the mouse; however, its immunoregulatory role in this tissue has not been explored. Herein, we show that 12/15-LOX is expressed by 95% of resident peritoneal CD11bhigh cells, with the remaining 5% being 12/15-LOX–. 12/15-LOX+ cells are phenotypically defined by high F4/80, SR-A, and Siglec1 expression, and enhanced IL-10 and G-CSF generation. In contrast, 12/15-LOX– cells are a dendritic cell population. Resident peritoneal Mφ numbers were significantly increased in 12/15-LOX–/– mice, suggesting alterations in migratory trafficking or cell differentiation in vivo. In vitro, Mφ from 12/15-LOX–/– mice exhibit multiple abnormalities in the regulation of cytokine/growth factor production both basally and after stimulation with Staphylococcus epidermidis cell-free supernatant. Resident adherent cells from 12/15-LOX–/– mice generate more IL-1, IL-3, GM-CSF, and IL-17, but less CCL5/RANTES than do cells from wild-type mice, while Staphylococcus epidermidis cell-free supernatant-elicited 12/15-LOX–/– adherent cells release less IL-12p40, IL-12p70, and RANTES, but more GM-CSF. This indicates a selective effect of 12/15-LOX on peritoneal cell cytokine production. In acute sterile peritonitis, 12/15-LOX+ cells and LOX products were cleared, then reappeared during the resolution phase. The peritoneal lavage of 12/15-LOX–/– mice showed elevated TGF-β1, along with increased immigration of monocytes/Mφ, but decreases in several cytokines including RANTES/CCL5, MCP-1/CCL2, G-CSF, IL-12-p40, IL-17, and TNF-α. No changes in neutrophil or lymphocyte numbers were seen. In summary, endogenous 12/15-LOX defines the resident MΦ population and regulates both the recruitment of monocytes/Mφ and cytokine response to bacterial products in vivo.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Biosciences
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 18 Oct 2022 14:29
URI: https://orca.cardiff.ac.uk/id/eprint/17683

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