Platelet-activating factor induces lung inflammation and leak in rats: hydrogen peroxide production along neutrophil-lung endothelial cell interfaces.
Interleukin-1 (IL-1) levels and neutrophils are increased in the lung-lavage fluid of patients with acute lung injury (ALI), and instilling IL-1 intratracheally into rats causes rapid lung-neutrophil influx and neutrophil-dependent lung leakage. IL-1 insufflation also increases platelet-activating factor (PAF) activity in rat lung, and PAF is increased in the lung-lavage fluid of ALI patients. To assess the direct effects of PAF on the lung, we administered PAF intratracheally in rats. We found that rats given PAF (5 microg) intratracheally had increased lung nuclear factor-kappaB activation, myeloperoxidase activity, numbers of lavage neutrophils, lavage neutrophil nitroblue tetrazolium reduction, and leakage compared with sham-treated rats administered saline solution intratracheally. Electron microscopic examination also indicated that lungs from rats given PAF intratracheally had increased neutrophil infiltration, cell damage, and neutrophil-endothelial cell interface cerium chloride staining - a marker of hydrogen peroxide production - compared with sham-treated rats. Simultaneous treatment with a PAF receptor-antagonist, WEB 2086, decreased the aforementioned changes observed after intratracheal administration of PAF.
Lee
Young M
YM
Webb Waring Institute for Cancer, Aging, and Antioxidant Research, University of Colorado Health Sciences Center, Denver, USA.
Hybertson
Brooks M
BM
Cho
Hyun G
HG
Repine
John E
JE
D000818:Animals; D001381:Azepines / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D002452:Cell Count; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D006861:Hydrogen Peroxide / Q000378:metabolism; D007365:Intercellular Junctions / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D009195:Peroxidase / Q000096:biosynthesis; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000627:therapeutic use
D001381:Azepines; D016328:NF-kappa B; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D006861:Hydrogen Peroxide; D009195:Peroxidase