Transgenic Mice Expressing Human Proteinase 3 Exhibit Sustained Neutrophil-Associated Peritonitis.

Martin, Katherine R; Pederzoli-Ribeil, Magali; Pacreau, Emeline; Burgener, Sabrina S; Dahdah, Albert; Candalh, Céline; Lauret, Evelyne; Foretz, Marc; Mouthon, Luc; Lucas, Bruno; Thieblemont, Nathalie; Benarafa, Charaf; Launay, Pierre; Witko-Sarsat, Véronique (2017). Transgenic Mice Expressing Human Proteinase 3 Exhibit Sustained Neutrophil-Associated Peritonitis. Journal of immunology, 199(11), pp. 3914-3924. American Association of Immunologists 10.4049/jimmunol.1601522

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Proteinase 3 (PR3) is a myeloid serine protease expressed in neutrophils, monocytes, and macrophages. PR3 has a number of well-characterized proinflammatory functions, including cleaving and activating chemokines and controlling cell survival and proliferation. When presented on the surface of apoptotic neutrophils, PR3 can disrupt the normal anti-inflammatory reprogramming of macrophages following the phagocytosis of apoptotic cells. To better understand the function of PR3 in vivo, we generated a human PR3 transgenic mouse (hPR3Tg). During zymosan-induced peritonitis, hPR3Tg displayed an increased accumulation of neutrophils within the peritoneal cavity compared with wild-type control mice, with no difference in the recruitment of macrophages or B or T lymphocytes. Mice were also subjected to cecum ligation and puncture, a model used to induce peritoneal inflammation through infection. hPR3Tg displayed decreased survival rates in acute sepsis, associated with increased neutrophil extravasation. The decreased survival and increased neutrophil accumulation were associated with the cleavage of annexin A1, a powerful anti-inflammatory protein known to facilitate the resolution of inflammation. Additionally, neutrophils from hPR3Tg displayed enhanced survival during apoptosis compared with controls, and this may also contribute to the increased accumulation observed during the later stages of inflammation. Taken together, our data suggest that human PR3 plays a proinflammatory role during acute inflammatory responses by affecting neutrophil accumulation, survival, and the resolution of inflammation.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Burgener, Sabrina S and Benarafa, Charaf

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0022-1767

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

28 Mar 2018 14:55

Last Modified:

29 Mar 2018 06:34

Publisher DOI:

10.4049/jimmunol.1601522

PubMed ID:

29079698

BORIS DOI:

10.7892/boris.112051

URI:

https://boris.unibe.ch/id/eprint/112051

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