Pharmacological modulation of lipopolysaccharide-induced pleural eosinophilia in the rat; a role for a newly generated protein.
Intrathoracic injection of endotoxin lipopolysaccharide, LPS into rats induced a dose-dependent increase in the number of eosinophils recovered from the pleural cavity. The pleural eosinophil accumulation peaked within 24-48 h, and returned to basal levels within 120 h. This phenomenon was accompanied by mononuclear cell infiltration, and preceded by massive neutrophil accumulation. Pretreatment with indomethacin, BW 755C (a dual cyclo/lipoxygenase inhibitor), BW A4C (a specific lipoxygenase inhibitor) or the platelet activating factor (PAF) antagonists WEB 2086 and PCA 4248 failed to inhibit the endotoxin-induced pleural eosinophilia, whilst dexamethasone (5-10 micrograms/cavity) or cycloheximide (14-28 micrograms/cavity) abolished this phenomenon. Transfer of the cell-free pleural washing from LPS-treated donor rats to normal recipient rats led to a two-fold increase in the eosinophil counts. Treatment of donors, but not recipients, with cycloheximide or dexamethasone inhibited the eosinophil accumulation induced by the pleural washings, indicating that the generation of the eosinophilotactic activity, but not its effects, depends on protein synthesis. This eosinophilotactic activity was maintained after lyophilization and heating (100 degrees C for 30 min), but was destroyed by trypsin. This substance has a molecular weight ranging between 10 and 50 kDa. The available data suggest that the late eosinophil accumulation induced by LPS is independent of arachidonic acid metabolites and PAF, and probably depends on a newly generated heat-stable soluble protein.
Bozza
P T
PT
Departamento di Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, Brazil.
Castro-Faria-Neto
H C
HC
Martins
M A
MA
Larangeira
A P
AP
Perales
J E
JE
e Silva
P M
PM
Cordeiro
R S
RS
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects*; D004926:Escherichia coli / Q000378:metabolism*; D005260:Female; D006358:Hot Temperature; D006868:Hydrolysis; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008970:Molecular Weight; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D010994:Pleura / Q000166:cytology* / Q000187:drug effects; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin; D014462:Ultrafiltration
D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011506:Proteins; D003907:Dexamethasone; D003513:Cycloheximide; D014357:Trypsin