title: Eosinophil accumulation in the rat pleural cavity after mast cell stimulation with compound 48/80 involves protein synthesis and is selectively suppressed by dexamethasone.
abstract: Alterations in the local mast cell population and the eosinophil accumulation in the rat pleural cavity were studied using pleurisy induced by compound 48/80, a standard mast-cell-degranulating agent. Twenty-four hours after the intrathoracic injection of compound 48/80 (1-50 micrograms/cavity), a dose-dependent eosinophil enrichment of the exudate was noted, concomitantly with a drastic reduction in the total number of undamaged mast cells recovered from the pleural washing. At 24 h, neutrophil counts were not modified, and the number of mononuclear cells was increased, but only at the highest dose of compound 48/80. The temporal analysis showed that mast cell degranulation, exudation and neutrophil infiltration were maximal at the interval of 1-6 h after compound 48/80 (25 micrograms/cavity), whereas eosinophil accumulation peaked within 24 h, persisting elevated at least until 96 h. Since compound 48/80 was itself unable to induce eosinophil migration in vitro, attempts were made to investigate the potential involvement of recognized eosinophil chemo-attractants, such as histamine, leukotriene B4 (LTB4) and platelet-activating factor (PAF-acether). The intraperitoneal pretreatment with either cyproheptadine (2 mg/kg), meclizine (40 mg/kg), BW755C (25 mg/kg) or with the PAF-acether receptor antagonist WEB 2086 (20 mg/kg) had no effect on the eosinophil recruitment induced by compound 48/80 (25 micrograms/cavity). However, the treatment with the corticosteroid dexamethasone or the local inhibition of protein biosynthesis with cycloheximide (0.04-200 nmol/cavity) blocked the eosinophil pleural accumulation, but not the mast cell degranulation induced by compound 48/80. Our findings indicate that the pleural eosinophil accumulation induced by compound 48/80 is sensitive to dexamethasone, requires local protein biosynthesis and is independent of histamine, LTB4 and PAF-acether.
authors.affiliation: Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Martins
authors.forename: C P
authors.initials: CP
authors.lastname: Pasquale
authors.forename: P M
authors.initials: PM
authors.lastname: e Silva
authors.forename: R S
authors.initials: RS
authors.lastname: Cordeiro
authors.forename: B B
authors.initials: BB
authors.lastname: Vargaftig
mesh_terms: D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects* / Q000473:pathology; D005260:Female; D007958:Leukocyte Count; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000473:pathology; D010972:Platelet Activating Factor / Q000494:pharmacology; D010994:Pleura / Q000473:pathology*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014230:Triazoles / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
chemical_list: D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D003189:p-Methoxy-N-methylphenethylamine; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D003907:Dexamethasone; D003513:Cycloheximide