Open AccessMatrix metalloproteinase‐3 production by gut IgG plasma cells in chronic inflammatory bowel disease
Author(s) -
Gordon John N.,
Pickard Karen M.,
Di Sabatino Antonio,
Prothero Joanna D.,
Pender Sylvia L.F.,
Goggin Patrick M.,
MacDonald Thomas T.
Publication year - 2008
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.20302
Subject(s) - elispot , inflammatory bowel disease , immunology , ulcerative colitis , lamina propria , cytokine , peripheral blood mononuclear cell , tissue inhibitor of metalloproteinase , medicine , biology , matrix metalloproteinase , immune system , in vitro , pathology , t cell , disease , epithelium , biochemistry
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 TGFβ, whereas they did not contain significant transcripts for IL‐4, IL‐5, IL‐10, IFNγ, 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)