Synovial tissue hypoxia and inflammation in vivo.

Hdl Handle:
http://hdl.handle.net/10147/207597
Title:
Synovial tissue hypoxia and inflammation in vivo.
Authors:
Ng, C T; Biniecka, M; Kennedy, A; McCormick, J; Fitzgerald, O; Bresnihan, B; Buggy, D; Taylor, C T; O'Sullivan, J; Fearon, U; Veale, D J
Affiliation:
Dublin Academic Medical Centre, St Vincent's University Hospital, Elm Park,, Dublin 4, Ireland.
Citation:
Ann Rheum Dis. 2010 Jul;69(7):1389-95. Epub 2010 May 3.
Journal:
Annals of the rheumatic diseases
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207597
DOI:
10.1136/ard.2009.119776
PubMed ID:
20439288
Abstract:
INTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.
Language:
eng
MeSH:
Adult; Aged; Aged, 80 and over; Arthritis, Psoriatic/blood/complications/*pathology; Arthritis, Rheumatoid/blood/complications/*pathology; *Cell Hypoxia/physiology; Cell Line; Chemokines/blood; Cytokines/blood; Humans; Middle Aged; Oxygen/blood; Partial Pressure; Synovial Membrane/*pathology; Synovitis/blood/etiology/*pathology
ISSN:
1468-2060 (Electronic); 0003-4967 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorNg, C Ten_GB
dc.contributor.authorBiniecka, Men_GB
dc.contributor.authorKennedy, Aen_GB
dc.contributor.authorMcCormick, Jen_GB
dc.contributor.authorFitzgerald, Oen_GB
dc.contributor.authorBresnihan, Ben_GB
dc.contributor.authorBuggy, Den_GB
dc.contributor.authorTaylor, C Ten_GB
dc.contributor.authorO'Sullivan, Jen_GB
dc.contributor.authorFearon, Uen_GB
dc.contributor.authorVeale, D Jen_GB
dc.date.accessioned2012-02-01T10:32:26Z-
dc.date.available2012-02-01T10:32:26Z-
dc.date.issued2012-02-01T10:32:26Z-
dc.identifier.citationAnn Rheum Dis. 2010 Jul;69(7):1389-95. Epub 2010 May 3.en_GB
dc.identifier.issn1468-2060 (Electronic)en_GB
dc.identifier.issn0003-4967 (Linking)en_GB
dc.identifier.pmid20439288en_GB
dc.identifier.doi10.1136/ard.2009.119776en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207597-
dc.description.abstractINTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshArthritis, Psoriatic/blood/complications/*pathologyen_GB
dc.subject.meshArthritis, Rheumatoid/blood/complications/*pathologyen_GB
dc.subject.mesh*Cell Hypoxia/physiologyen_GB
dc.subject.meshCell Lineen_GB
dc.subject.meshChemokines/blooden_GB
dc.subject.meshCytokines/blooden_GB
dc.subject.meshHumansen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshOxygen/blooden_GB
dc.subject.meshPartial Pressureen_GB
dc.subject.meshSynovial Membrane/*pathologyen_GB
dc.subject.meshSynovitis/blood/etiology/*pathologyen_GB
dc.titleSynovial tissue hypoxia and inflammation in vivo.en_GB
dc.contributor.departmentDublin Academic Medical Centre, St Vincent's University Hospital, Elm Park,, Dublin 4, Ireland.en_GB
dc.identifier.journalAnnals of the rheumatic diseasesen_GB
dc.description.provinceLeinster-
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