Molecular determinants of monosodium urate crystal-induced murine peritonitis: a role for endogenous mast cells and a distinct requirement for endothelial-derived selectins.
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 (approximately 10 x 10[6] 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 microg 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.
Getting
S J
SJ
Department of Biochemical Pharmacology, The William Harvey Research Institute, London, United Kingdom.
Flower
R J
RJ
Parente
L
L
de Medicis
R
R
Lussier
A
A
Woliztky
B A
BA
Martins
M A
MA
Perretti
M
M
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003460:Crystallization; D004730:Endothelium, Vascular / Q000502:physiology*; D006073:Gout / Q000188:drug therapy; D006632:Histamine / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010538:Peritonitis / Q000139:chemically induced*; D010972:Platelet Activating Factor / Q000502:physiology; D019087:Selectins / Q000502:physiology*; D014527:Uric Acid / Q000494:pharmacology*
D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D019087:Selectins; D014527:Uric Acid; D006632:Histamine