title: Platelet-activating factor contributes to acute lung leak in rats given interleukin-1 intratracheally.
abstract: Lung lavage fluid of patients with acute lung injury (ALI) has increased levels of interleukin-1 (IL-1) and neutrophils, but their relationship to the lung leak that characterizes these patients is unclear. To address this concern, we investigated the role of the neutrophil agonist platelet-activating factor [1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF)] in the development of the acute neutrophil-dependent lung leak that is induced by giving IL-1 intratracheally to rats. We found that PAF acetyltransferase and PAF activities increased in lungs of rats given IL-1 intratracheally compared with lungs of sham-treated rats given saline intratracheally. The participation of PAF in the development of lung leak and lung neutrophil accumulation after IL-1 administration was suggested when treatment with WEB-2086, a commonly used PAF-receptor antagonist, decreased lung leak, lung myeloperoxidase activity, and lung lavage fluid neutrophil increases in rats given IL-1 intratracheally. Additionally, neutrophils recovered from the lung lavage fluid of rats given IL-1 intratracheally reduced more nitro blue tetrazolium (NBT) in vitro than neutrophils recovered from control rats or rats that had been given WEB-2086 and then IL-1. Histological examination indicated that the endothelial cell-neutrophil interfaces of cerium chloride-stained lung sections of rats given IL-1 contained increased cerium perhydroxide (the reaction product of cerium chloride with hydrogen peroxide) compared with lungs of control rats or rats treated with WEB-2086 and then given IL-1 intratracheally. These in vivo findings were supported by parallel findings showing that WEB-2086 treatment decreased neutrophil adhesion to IL-1-treated cultured endothelial cells in vitro. We concluded that PAF contributes to neutrophil recruitment and neutrophil activation in lungs of rats given IL-1 intratracheally.
authors.affiliation: Webb Waring Institute for Cancer, Aging, and Antioxidant Research at the University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: Y M
authors.initials: YM
authors.lastname: Lee
authors.forename: B M
authors.initials: BM
authors.lastname: Hybertson
authors.forename: H G
authors.initials: HG
authors.lastname: Cho
authors.forename: L S
authors.initials: LS
authors.lastname: Terada
authors.forename: O
authors.initials: O
authors.lastname: Cho
authors.forename: A J
authors.initials: AJ
authors.lastname: Repine
authors.forename: J E
authors.initials: JE
authors.lastname: Repine
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D007202:Indicators and Reagents / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007442:Intubation, Intratracheal; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010539:Permeability; D010972:Platelet Activating Factor / Q000378:metabolism / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D007202:Indicators and Reagents; D007375:Interleukin-1; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D009580:Nitroblue Tetrazolium