Increased migration of neutrophils to granulocyte-colony stimulating factor in rat carrageenin-induced pleurisy: roles of complement, bradykinin, and inducible cyclooxygenase-2.
Administration of human recombinant granulocyte colony-stimulating factor (G-CSF, 100 micrograms/kg/day, s.c) to rats for 4 days significantly increased circulating neutrophil counts (by 1130%), together with an increase in mononuclear leukocyte counts (by 119%). Infiltrated pleural neutrophil counts in G-CSF-treated rats (G-CSF-r) 5 h after the intrapleural injection of zymosan-activated serum were significantly higher (by 155%) than those in control rats (Vehicle-r). In carrageenin-induced pleurisy, counts of infiltrated pleural neutrophils in G-CSF-r 5 and 7 h after carrageenin were significantly higher (by 119% and 116%) than those in Vehicle-r. G-CSF treatment increased the volume of pleural exudate and the plasma exudation rate by 122% and 226%, compared to values in Vehicle-r 5 h after carrageenin. Cobra venom factor (75 micrograms/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 exudate volume and plasma exudation. Intrapleural bradykinin-(1-5) and prostaglandin E2 levels were significantly higher in G-CSF-r than in Vehicle-r. The increased neutrophil migration in G-CSF-r may be attributed to enhanced activation of the complement system facilitated by increased plasma exudation due to bradykinin and prostaglandins.
Ogino
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Majima
M
M
Kawamura
M
M
Hatanaka
K
K
Saito
M
M
Harada
Y
Y
Katori
M
M
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000502:physiology*; D002199:Capillary Permeability; D002351:Carrageenan / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D003165:Complement System Proteins / Q000502:physiology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000032:analysis; D004546:Elapid Venoms / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010998:Pleurisy / Q000097:blood*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D004546:Elapid Venoms; D007527:Isoenzymes; D008565:Membrane Proteins; D011994:Recombinant Proteins; C016310:cobra venom factor; D016179:Granulocyte Colony-Stimulating Factor; D002351:Carrageenan; D003165:Complement System Proteins; D015054:Zymosan; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin; D001920:Bradykinin