Matrix metalloproteinase-3 production by gut IgG plasma cells in chronic inflammatory bowel disease

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http://www3.interscience.wiley.com/cgi-bin/abstract/116845318/ABSTRACT?CRETRY=1 & SRETRY=0

Original Article

Matrix metalloproteinase-3 production by gut IgG plasma cells in chronic inflammatory bowel disease

N. Gordon, DM, MRCP 1 2 3 *, M. Pickard, PhD 1 2 3, Di Sabatino, MD 1 2 3, Joanna D. Prothero, DM, MRCP 1 2 3, Sylvia L.F. Pender, PhD 1 2 3, M. Goggin, DM, MRCP 2, T. Mac, PhD 3

1Division of Infection, Inflammation and Repair, University of Southampton, School of Medicine, Southampton, UK2Department of Gastroenterology, Queen andra Hospital, Cosham, Portsmouth, UK3Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, UK

email: N. Gordon (jngordon@...)

*Correspondence to N. Gordon, Department of Gastroenterology, Southampton University Hospital Trust, Southampton, SO16 6YD, UK

Data from this study were presented as an oral presentation at the UEGW in Berlin in 2006, Gut 2006;55(Suppl V):A31, at the 5th European Mucosal Immunology Meeting in Prague 2006; as an oral presentation at the British Society of Gastroenterology Annual meeting in Birmingham in 2006, Gut 2006;55(Suppl II):A16-061; at the Digestive Diseases Week in Chicago in May 2005, Gastroenterology 2005;128(Suppl 2):A504; and at the British Society of Gastroenterology Annual Meeting in 2005, Gut 2005;54(Suppl II):A97-368.

Keywords

Crohn's disease • cytokines • matrix metalloproteinase • plasma cell • ulcerative colitis

Abstract

Background: In both ulcerative colitis (UC) and Crohn's disease (CD) there is a marked increase in mucosal IgG plasma cells (PC), although their precise role is not well established. In this study we isolated gut PCs from patients with IBD and normal controls and analyzed cytokine production, matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 production, and PC longevity ex vivo.

Methods: Lamina propria mononuclear cells (LPMCs) were isolated from patients with CD (n = 19), UC (n = 27), and normal controls (n = 42). PCs were further selected by immunomagnetic isolation using CD138 microbeads. Cytokine, MMP-3, and TIMP-1 expression was investigated by Taqman polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and confocal microscopy. PC lifespan in vitro was studied by ELISpot analysis.

Results: PCs from both controls and IBD patients contained high levels of transcripts for TGF, whereas they did not contain significant transcripts for IL-4, IL-5, IL-10, IFN, TNF, or IL-12p40. PCs from patients with CD and UC expressed significantly higher levels of MMP-3 protein and transcripts than controls (P < 0.0001). The vast majority of MMP-3-expressing PCs were IgG+ve. In culture, IgA PCs from both IBD patients and controls persisted for only a few days, but IgG PCs from IBD patients persisted for at least 3 weeks.

Conclusions: We have demonstrated that IgG PCs from patients with IBD express large amounts of MMP-3 and that they appear to be long-lived. These results identify a new pathway by which IgG PCs may damage the gut.

(Inflamm Bowel Dis 2007, Volume 14, Issue 2 , Pages 195 - 203 )

Received: 6 September 2007; Accepted: 7 September 2007

Digital Object Identifier (DOI)10.1002/ibd.20302