Generation of an eosinophilotactic activity in the pleural cavity of platelet-activating factor-injected rats.
The injection of platelet-activating factor (PAF) into the rat pleural cavity resulted in a marked increase in the number of eosinophils, neutrophils and mononuclear cells recovered from pleural washings after 6 hr. Within 24 hr, neutrophils and mononuclear cell counts returned to control values, whereas the eosinophilia peaked and persisted up to 96 hr. Treatment with the PAF antagonist BN 52021 [3-(1,1-dimethylethyl)hexahydro-1,4,7b-trihydroxy-8-alpha-methyl-9H-1,7- alpha-(epoxymethanol)1H,6aH-cyclopenta (c) furo (2,3-5) (3',2':3,4) cyclopenta (1,2-d) furan-5,9,12(4H)trione)] (5-20 micrograms/cavity) or with dexamethasone (1-50 micrograms/cavity) inhibited the early (6 hr) and late (24 hr) pleural eosinophil accumulation induced by PAF. Dexamethasone, but not BN 52021, was still effective in inhibiting the late eosinophilia if administered 5 hr after the lipid, suggesting that the delayed eosinophilia may involve a secondary mechanism, still responsive to the glucocorticoid, but independent of PAF itself. The coinjection of the protein synthesis inhibitor cycloheximide or of the inhibitor of mRNA synthesis DNA-dependent actinomycin D selectively suppressed the eosinophil mobilization at 24 hr. Transfer of the cell-free 6-hr PAF pleural washing from donor to normal recipient rats led to a selective and delayed pleural eosinophilia. This activity was destroyed by heating (+100 degrees C) or freezing (-20 degrees C) the material recovered from the donor pleural fluid. Treatment of donors, but not recipients, with either BN 25021, dexamethasone, actinomycin D or cycloheximide inhibited the late eosinophil accumulation triggered by transferred PAF pleural washing, indicating that the generation of this eosinophilotactic activity, but not its effects, is suppressed by those agents.(ABSTRACT TRUNCATED AT 250 WORDS)
e Silva
P M
PM
Departmento de Fisiologia e Farmacodinâmica, IOC, FIOCRUZ Av. Brasil, Rio de Janeiro.
Martins
M A
MA
Faria Neto
H C
HC
Cordeiro
R S
RS
Vargaftig
B B
BB
D000818:Animals; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004224:Diterpenes; D004355:Drug Stability; D004804:Eosinophils / Q000187:drug effects; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010994:Pleura / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature
D002631:Chemotactic Factors, Eosinophil; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide; C045856:ginkgolide B