A. Dunky et al., INTERACTIONS OF LYMPHOCYTES FROM PATIENTS WITH PSORIATIC-ARTHRITIS ORHEALTHY CONTROLS AND CULTURED ENDOTHELIAL-CELLS, Clinical immunology and immunopathology, 85(3), 1997, pp. 297-314
Psoriatic arthritis (PA) is an inflammatory rheumatic disease that can
concomitantly occur in patients with psoriasis vulgaris. Psoriatic sy
novitis shows alterations of the synovial microvasculature. Inflammato
ry cells adhere to endothelial cells (EC) and migrate through the vasc
ular wall of postcapillary venules located in the subintimal layer of
the synovial membrane. The aim of our study was to investigate, first,
the phenotype of lymphocytes (LC) of PA patients using flow cytometry
(FC) with regard to activation antigens and adhesion molecules; secon
d, the adhesion of LC of PA patients on cultivated resting or activate
d (with thrombin, LPS, IFN-gamma, or TNF-alpha) human umbilical vein e
ndothelial cells (HUVEC) by counting the Feulgen-stained nuclei of bot
h adherent LC and HUVEC using image analysis; and third, the synthesis
of IL-6 and IL-8 in both LC and HUVEC 24 hr after cell contact. These
cytokines were determined qualitatively by immunofluorescence and qua
ntitatively at the single-cell level by FC as well as in the supernata
nts of the cultures using commercial cytokine ELISAs. Fourth, we inves
tigated whether or not the LC adhesion on HUVEC as well as the cytokin
e production could be inhibited by monoclonal antibodies against LC-or
EC-specific adhesion molecules. In contrast to controls PA patients s
howed an increased surface expression of CD11a, b, and c as well as of
CD44 but a reduced surface expression of CD49d/CD29, CD49e/CD29, and
cell-bound fibronectin on CD3(+) LC. The activation markers CD25 and H
LA-DR were found to be slightly enhanced in PA The cell adhesion was g
enerally enhanced in PA patients vs controls. It could be reduced with
monoclonal antibodies (MoAbs) against CD11a and CD18 on IFN-gamma- or
TNF-alpha-activated HUVEC but was generally enhanced after treatment
of HUVEC with MoAbs against CD54, CD62E, or CD106. Due to LC adhesion
on HUVEC IL-6 and IL-8 were produced in significantly higher amounts i
n PA patients compared to controls. This effect occurred already in re
sting but was enhanced in activated HUVEC. While IL-6 is mainly produc
ed by HUVEC but also in smaller quantities by LC, IL-8 is synthesized
only by HUVEC and could be modified by preincubation with MoAbs agains
t LC-or EC-specific adhesion molecules in parallel to the cell adhesio
n. The experiments show that the main adhesion pathway in LC homing of
PA patients is the interaction of the LC adhesion molecule CD11a/CD18
with CD54 on EC followed by an enhanced synthesis of proinflammatory
and chemotactic cytokines. These results favor the hypothesis that the
pathological alterations of the microvasculature in PA patients are g
enerated by altered homing processes. (C) 1997 Academic Press.