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Vol. 283, Issue 1, 123-130, 1997
Department of Biochemical Pharmacology, The William Harvey Research
Institute, London, United Kingdom (S.J.G., R.J.F., M.A.M., M.P.);
Istituto di Farmacologia e Farmacognosia, Facolt[aa]a di Farmacia,
Palermo, Italy (L.P.);
Rheumatic Disease Unit, Faculty of Medicine,
Université de Sherbrooke, Sherbrooke, Canada (R.d.M., A.L.);
Department of Inflammation/Autoimmune Diseases, Hoffman-La Roche Inc.,
Nutley, New Jersey (B.A.W.)
Injection of monosodium urate (MSU) crystals, the etiological cause of
gouty arthritis, into murine peritoneal cavities produced an intense
recruitment of polymorphonuclear leukocytes (PMN). After 3 mg MSU
crystal injection, cell influx was maximal (~ 10 × 106 cells per mouse) at 6 hr postinjection and sustained up
to the 24 hr time-point. In mice depleted of mast cells by
administration of compound 48/80 72 hr before challenge with MSU
crystals a lower PMN influx was measured (58% reduction). The
occurrence of endogenous mast cell activation, in the MSU response, was
validated by the observation that MSU challenge reduced by more than
90% the number of intact mast cells recovered in the peritoneal
washes. Pretreatment of mice with a histamine H1 antagonist
(tripolidine; 0.5 mg/kg) or a platelet-activating factor receptor
antagonist (WEB2086; 10 mg/kg) significantly reduced by 50 to 60% the
number of PMN recovered from the peritoneal cavities. The molecular
determinants of this process of leukocyte recruitment were also
investigated. Treatment of mice with an anti-CD62P or anti-CD62E
monoclonal antibody (mAb; 100 µg i.v.) produced a distinct inhibition
of PMN recruitment measured at 6 hr, whereas only a combined
administration of both monoclonal antibodies was effective in reducing
by 60% the influx of PMN caused by the MSU crystals within 24 hr. In conclusion, these data highlight a role for endogenous mast cells and
for endothelial-derived selectins in MSU crystal-induced PMN recruitment into the peritoneal cavity, and may be useful to dissect molecular mechanism(s) which may be operating in gouty arthritis.
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