INCREASED MIGRATION OF NEUTROPHILS TO GRANULOCYTE-COLONY-STIMULATING FACTOR IN RAT CARRAGEENAN-INDUCED PLEURISY - ROLES OF COMPLEMENT, BRADYKININ, AND INDUCIBLE CYCLOOXYGENASE-2

Administration of human recombinant granulocyte colony-stimulating fac tor (G-CSF, 100 mu g/kg/day, s.c) to rats for 4 days significantly inc reased circulating neutrophil counts (by 1130%), together with an incr ease in mononuclear leukocyte counts (by 119%). Infiltrated pleural ne utrophil counts in G-CSF-treated rats (G-CSF-r) 5 h after the intraple ural injection of zymosan-activated serum were significantly higher (b y 155%) than those in control rats (Vehicle-r). In carrageenin-induced pleurisy, counts of infiltrated pleural neutrophils in G-CSF-r 5 and 7h after carrageenin were significantly higher (by 119% and 116%) than those in Vehicle-r. G-CSF treatment increased the volume of pleural e xudate and the plasma exudation rate by 122% and 226%, compared to val ues in Vehicle-r 5h after carrageenin. Cobra venom factor (75 mu g/kg, i.v.) significantly reduced pleural neutrophil migration in G-CSF-r ( by 53%) and Vehicle-r (by 49%). Bromelain (10 mg/kg, i.v.) and aspirin (100 mg/kg, p.o.) reduced pleural neutrophil migration and reduced ex udate volume and plasma exudation. Intrapleural bradykinin-(1-5) and p rostaglandin E(2) levels were significantly higher in G-CSF-r than in Vehicle-r. The increased neutrophil migration in G-CSF-r may be attrib uted to enhanced activation of the complement system facilitated by in creased plasma exudation due to bradykinin and prostaglandins.