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b u r
7
J
ecreased CDllb expression
circulating polymorphonuclear leukocytes
patients with extensive plaque psoriasis
Jan P.A. van
Piet E J. van ERP
Peter C.M. van de KE
In
psoriatic lesion
integriti receptor Mac
an. important
tio n s
extravasation, tissue migration and
investigated the possibility o f systemic
sion *
Venous blood samples were obtained from
Index greater than 10.0)
unstim ulated
matched, healthy controls
leukocytes were
flow cytometry methods
sion was observed
su b je c ts. A fter
difference
w r
./muni
» IW <<U <HU»
*
.'.P.A. van Pelt
Fax: (+31) 24.35.41.184.
E-mail: [email protected]
utaee ous
'W
individual
have even
relation
the P A S I-sco re
C D llb T
.
T
n,
...
t
./CDllb
was
LI o
sti m u !¿ttc^ci
ti n sti 111u Icit cci
pathway
retore,
C D llb expression
C
s
D
i
s
l
.
l
b
,
f
l
o
w
)
is an
aspect of the
Already in pinpoint psoriatic
zone of the margin of psoriatic
treatment, accumulation of T-lymphocytes, monocytes, mast
cells and polymorphonuclear leukocytes (PMM) can be obser­
ved [ ! ]. No substantial inflammatory changes have been seen
in the
from the psoriatic lesion,
some
of T-lympho. Until now, no consensus
been reached on
which cells are first in invading the “pre-psoriatic skin
The invasion
in
is an early feature. The epidermal accumulation
Q
of pon
the stratum Malpighi, and micro
abcesses of Munro as intracorneal accumulations
psoriasis, PMN accumulation is the dominating feature [5, 6]
In peripheral blood, functional and biochemical
tion has revealed normal, decreased and increased expression
or
activation
[7]. The activity of the psoriatic
process whether expanding or stable proved to be an impor-
«
are of great
cellular and cell-matrix interactions
non-covf
ß-chain
integri n
.È
of
of
*<W
vas
vasation
.1n d
la tio n .
The
receptor can
mical compounds such
vating factor,
the best of our knowledge
Mac
M tm
7
J?3M>
4
UfA
(LTB4)
r
>
Ob sO
< # >r"
produced in large quantities in psoriatic
LTB . which
formed
pote nt upre g u1ato i
r
i, d a t c
i*0#
We chose
T
t*
which
la i
other leukocyte subsets
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Basal Jtvel of neutrophil CDHb-s*preiilon
Figure 3. Correlation between the number o f CDl l b mole­
cules present on unstimulated peripheral blood PMN and the
increased number that is present on these PMN after in vitro
stimulation with LTB4>
considerably. However, in contrast to the difference with res­
pect to absolute values, the relative C D llb up-regulation was
virtually identical in patients and healthy subjects.
Experimental variability of flow cytometrical C D llb assess­
ment proved to be below 10% comparing the triplicate mea­
surements. Therefore, the present investigation reconfirms the
high experimental reproducibility of the methods used.
In patients and healthy volunteers, the C D llb-levels on
peripheral blood PMN following stimulation with LTB4 corre­
late with the basal levels of C D llb, as illustrated in Figure 3.
Therefore, unstimulated PMN CDl l b expression determines
LTB4-induced PMN CDl l b expression. The correlation bet­
ween unstimulated and stimulated CDllb-levels in psoriatic
patients and healthy controls seems to be comparable since
there is no difference in relative CD1 lb up-regulation between
both groups. This provides a strong indication that the signal­
ling from LTB4-receptor binding up to CDl l b expression on
peripheral blood PfylN is essentially normal in psoriasis.
The tendency to decreased basal expression of CDl l b and
the significantly decreased LTB4-induced psoriatic PMN
CDl l b expression compared to normal PMN indicates a
decreased number of CD1 lb-hemireceptors on psoriatic
PMN. The decreased expression of C D l l b on peripheral
blood PMN, further decreasing in unstable psoriasis, is in
sharp contrast with the in vitro chemotaxis and protease acti­
vity which increases in unstable psoriasis [8].
Three explanations for the decreased CDl l b expression of
circulating psoriatic PMN may be hypothesized: (1) compartmentalisation of PMN subpopulations; (2) habituation to
increased levels of leukotriene B4; (3) active down-modulation of CD1 lb-levels on psoriatic peripheral blood PMN.
The hypothesis of compartmentalisation of circulating blood
PMN is based on PMN subset selection. It is probable that
the PMN-subpopulation with the highest CD1 lb expression is
most likely to be recruited to invade the inflammed psoriatic
skin, whereas PMN with a more modest density of CDl l b
remain in the blood circulation. Indeed, patients with unstable
psoriasis proved to have an even lower CDl l b expression on
peripheral blood PMN than the overall group of psoriatic
patients, In active psoriatic lesions, PMN-influx has been
reported in 78% of patients and in chronic plaque lesions,
PMN-influx proved to occur in 41% of patients [27].
EJD n° 5, vol. 7, July-August 1997
An alternative explanation is habituation of peripheral blood
PMN to increased LTB4~levels present in psoriatic skin. This
hypothesis is supported by the observation that in psoriatic
uninvolved skin a decreased accumulation of PMN occurs
following a standardized stimulus with LTB4 [28, 29]. Repea­
ted LTB4 applications resulted in a decreased PMN accumu­
lation as compared to the response following a single applica­
tion [29]. However, in view of the fact that the relative
C D l l b up-regulation by LTB4 in psoriatics proved to be
essentially normal, this hypothesis is not supported by the
observations in the present study.
Active down-modulation of C D l l b is another possible
mechanism that could explain the decreased PMN C Dl l b
expression in psoriatic patients. It may be possible that such a
defence mechanism exists in order to prevent massive cuta­
neous damage due to the abundant skin presence of PMN. To
the best of our knowledge there are no known active downmodulators of CDl l b. However, integrin a-units, like CDl l b
need divalent cations (calcium or magnesium) for their adhe­
sive functions, and receptor function can be rapidly modula­
ted through phosphorylation reactions [9], It might well be
possible that C D l l b can be down-modulated on a functional
level by changes in cation-concentrations and phosphorylase
activity.
Since LTB4-induced signalling in psoriatic PMN is essentially
normal, the question arises as to what extent LTB4 is relevant
to the CDl l b up-regulation of psoriatic PMN in vivo. The
role of LTB4 in psoriasis has been challenged further by the
modest effects of 5-lipoxygenase inhibitors in the treatment
of psoriasis [30-33].
The decreased C D l l b expression on peripheral blood PMN in
psoriasis remains an intriguing finding, and further studies
should be aimed at mediators and factors involved in PMN
compartmentalisation in psoriasis, and at mechanisms invol­
ved in the in vivo regulation of CD1 lb in psoriatic patients. ■
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EJD n° 5, vol, 7, July-August 1997