Matrix metalloproteinase-3 production by gut IgG plasma cells in chronic inflammatory bowel disease.
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 TGFbeta, whereas they did not contain significant transcripts for IL-4, IL-5, IL-10, IFNgamma, 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.
Gordon
John N
JN
Division of Infection, Inflammation and Repair, University of Southampton, School of Medicine, Southampton, UK. jngordon@f2s.com
Pickard
Karen M
KM
Di Sabatino
Antonio
A
Prothero
Joanna D
JD
Pender
Sylvia L F
SL
Goggin
Patrick M
PM
MacDonald
Thomas T
TT
D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D016207:Cytokines; D007074:Immunoglobulin G; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3