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Tumour necrosis factor α stimulated rheumatoid synovial microvascular endothelial cells exhibit increased shear rate dependent leucocyte adhesion in vitro

Abstract

OBJECTIVE To investigate endothelial cell adhesion molecule expression and leucocyte adhesion to endothelial cells isolated from the microvasculature of rheumatoid arthritic synovial tissue (SMEC) in comparison with similar cells isolated from healthy subcutaneous adipose tissue (ADMEC) or from umbilical veins (HUVEC).

METHODS Cultured endothelial cells were treated with tumour necrosis factor α (TNFα) for 2–24 hours before the assessment of cell surface E-selectin, vascular (VCAM-1) or intercellular cell adhesion molecule-I (ICAM-1) expression. Neutrophil and T lymphocyte adhesion to TNFα treated endothelial cells was assessed using static and shear dependent assay systems.

RESULTS VCAM-1 expression by SMEC was significantly less sensitive to TNFα stimulation than HUVEC or ADMEC. E-selectin expression by SMEC appeared to be more sensitive to TNFα stimulation and maximal expression was about 30% greater in comparison with HUVEC or ADMEC. Sensitivity to TNFα induction and maximal ICAM-1 expression was similar in all three endothelial cell types. Static neutrophil adhesion to TNFα stimulated SMEC was significantly increased in comparison with HUVEC, however this phenomenon was dependent on the presence of neutralising antibodies to ICAM-1. At shear rates in excess of 2.4 dynes/cm2significantly more neutrophils and, predominantly CD45RO+, T lymphocytes adhered to TNFα stimulated SMEC than HUVEC.

CONCLUSION Rheumatoid synovial endothelial cells differentially regulate E-selectin and VCAM-1. The increased ability of TNFα stimulated synovial endothelial cells to support leucocyte adhesion may help to explain the leucocyte, in particular CD45RO+ T-lymphocyte, recruitment observed in the rheumatoid synovium.

  • endothelium
  • adhesion molecules
  • rheumatoid arthritis

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