Rapid mast cell activation causes polymorphonuclear leukocyte
dependent and independent permeability alterations in postcapillary
venules.
Kubes, Paul, and Jeffrey P. Gaboury.
Immunology Research Group, University of Calgary Medical Centre,
Calgary, Alberta, T2N 4N1
APStracts 3:0242H, 1996.
The major objective of this study was to systematically elucidate the
mechanisms underlying microvascular permeability in rat mesenteric
venules following the activation of perivascular mast cells.
Intravital microscopy was used to assess polymorphonuclear leukocyte
(PMN) infiltration and microvascular permeability alterations in
single 25-40 [mu]m diameter venules. Ruthenium red was used to detect
mast cell activation online. Exposure of mast cells to compound 48/80
(CMP 48/80) caused a rapid mast cell activation and increase in
microvascular permeability (within 15 min) which was maintained for
the duration of the experiment. Compound 48/80 also increased PMN
adhesion to the microvascular endothelium. Anti-PMN serum, as well as
various anti-adhesion therapies, including CL26 (anti-CD18 antibody)
and fucoidin (selectin-immunoneutralizing carbohydrate) revealed that
the early microvascular permeability was PMN-independent. However,
these regimens significantly reduced plasma protein leakage out of
venules between 30 and 60 min. Methysergide (serotonin receptor
antagonist), but not diphenhydramine (histamine receptor antagonist),
entirely inhibited the early PMN-independent microvascular
permeability. Finally, a PAF-receptor antagonist did not affect the
early phase of microvascular permeability, but reversed the later
phase consistent with PAF's role as a pro-adhesive molecule for PMNs
during mast cell activation. These data demonstrate that within the
first hour of mast cell activation, a biphasic PMN-independent and
dependent response in microvascular permeability is observed. The
data also raise the possibility that histamine's physiological role
in this model may be unrelated to alterations in microvascular
permeability.
Received 30 November 1995; accepted in final form 3 June 1996.
APS Manuscript Number H1114-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96