Lipopolysaccharide-induced pleural neutrophil accumulation depends on marrow neutrophils and platelet-activating factor.
The involvement of platelet-activating factor (PAF) in lipopolysaccharide (LPS)-induced leukocyte accumulation in the rat pleural cavity was investigated. Intrathoracic (i.t.) injection of LPS (250 ng/cavity) induced a marked increase in the number of neutrophils at 1 h, which was maximum within 6-12 h, reducing after 24 h. In parallel, an increase in blood neutrophil counts within 1-6 h, concomitantly with a reduction in the number of these cells in the bone marrow, was observed. The number of eosinophils recovered from LPS-injected pleural cavity increased at 12 h and was maximum within 24-48 h. No change in blood or bone marrow eosinophil counts was detected. The pretreatment with WEB 2086 or PCA 4248 (20 mg/kg) significantly inhibited pleural neutrophil accumulation, blood neutrophilia and the decrease in the marrow neutrophil content, but not eosinophil accumulation. The blood neutrophilia and the decrease in marrow neutrophil counts induced by the intravenous (i.v.) injection of LPS (250 ng) were significantly lower than those observed after i.t. injection. Furthermore, WEB 2086 and PCA 4248 were ineffective against the systemic alteration induced by i.v. LPS. it was concluded that LPS-induced neutrophil, but not eosinophil, accumulation in the pleural cavity is related to the mobilization of neutrophils from the bone marrow and involves PAF dependent mechanisms.
Departmento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, Brazil.
P T
PT
Bozza
H C
HC
Castro-Faria-Neto
A R
AR
Silva
A P
AP
Larangeira
P M
PM
Silva
M A
MA
Martins
R S
RS
Cordeiro
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002453:Cell Cycle; D002465:Cell Movement / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D007267:Injections; D007700:Kinetics; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D010994:Pleura / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013909:Thorax; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D004095:Dihydropyridines; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; C066024:PCA 4248