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

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 (HUVEC). Methods-Cultured endothelial. cells were treated with tumour necrosis factor alpha (TNF alpha) 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 TNF alpha treated endothelial cells was assessed using static and shear dependent assay systems. Results-VCAM-1 expression by SMEC was significantly less sensitive to TNF alpha stimulation than HUVEC or ADMEC. E-selectin expression by SMEC appeared to be more sensitive to TNF alpha stimulation and maximal expression was about 30% greater in comparison with. HUVEC or ADMEC. Sensitivity to TNF alpha induction and maximal ICAM-1 expression was similar in all three endothelial cell types. Static neutrophil adhesion to TNF alpha 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/cm(2) significantly more neutrophils and, predominantly CD45RO+, T lymphocytes adhered to TNF alpha stimulated SMEC than HUVEC. Conclusion-Rheumatoid synovial endothelial cells differentially regulate E-selectin and VCAM-1. The increased ability of TNF alpha 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.