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stimulated rheumatoid synovial
microvascular endothelial cells exhibit increased shear rate dependent
leucocyte adhesion in vitro
a Departments of
Pharmacy and Pharmacology, b Biochemistry, c Postgraduate Medicine, d and
Mathematical Sciences, e University of Bath, Bath
Correspondence to: Dr S E Abbot, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY.
Accepted for publication 4 May 1999
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
(TNF
)
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
treated
endothelial cells was assessed using static and shear dependent assay systems.
RESULTS
VCAM-1
expression by SMEC was significantly less sensitive to TNF
stimulation than HUVEC or ADMEC. E-selectin expression by SMEC appeared
to be more sensitive to TNF
stimulation and maximal expression was
about 30% greater in comparison with HUVEC or ADMEC. Sensitivity to
TNF
induction and maximal ICAM-1 expression was similar in all three
endothelial cell types. Static neutrophil adhesion to TNF
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/cm2
significantly more neutrophils and, predominantly CD45RO+, T lymphocytes adhered to TNF
stimulated SMEC than HUVEC.
CONCLUSION
Rheumatoid
synovial endothelial cells differentially regulate E-selectin and
VCAM-1. The increased ability of TNF
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.
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