LIPOPOLYSACCHARIDE-INDUCED PLEURAL NEUTROPHIL ACCUMULATION DEPENDS ONMARROW NEUTROPHILS AND PLATELET-ACTIVATING-FACTOR

The involvement of platelet-activating factor (PAF) in lipopolysacchar ide (LPS)-induced leukocyte accumulation in the rat pleural cavity was investigated. Intrathoracic (i.t.) injection of LPS (250 ng/cavity) i nduced a marked increase in the number of neutrophils at 1 h, which wa s maximum within 6-12 h, reducing after 24 h. In parallel, an increase in blood neutrophil counts within 1-6 h, concomitantly with a reducti on in the number of these cells in the bone marrow, was observed. The number of eosinophils recovered from LPS-injected pleural cavity incre ased at 12 h and was maximum within 24-48 h. No change in blood or bon e marrow eosinophil counts was detected. The pretreatment with WEB 208 6 or PCA 4248 (20 mg/kg) significantly inhibited pleural neutrophil ac cumulation, blood neutrophilia and the decrease in the marrow neutroph il content, but not eosinophil accumulation. The brood neutrophilia an d the decrease in marrow neutrophil counts induced by the intravenous (i.v:) injection of LPS (250 ng) were significantly lower than those o bserved after i.t. injection. Furthermore, WEB 2086 and PCA 4248 were ineffective against the systemic alteration induced by i.v. LPS. It wa s concluded that LPS-induced neutrophil, but not eosinophil, accumulat ion in the pleural cavity is related to the mobilization of neutrophil s from the bone marrow and involves PAF dependent mechanisms.