title: Mepacrine decreases lung leak in rats given interleukin-1 intratracheally.
abstract: We hypothesized that phospholipase A2 (PLA2) metabolites contribute to the acute, neutrophil-dependent, edematous lung leak that develops after administration of interleukin-1 (IL-1) intratracheally to rats and tested this premise by using mepacrine to inhibit PLA2 activity in vivo. We found that lung PLA2 activity, lung lavage phospholipid content, lung leak index, lung weight gain, and lung lavage protein concentrations were increased in rats given IL-1 intratracheally compared with sham-treated control rats. By comparison, lungs of mecaprine and IL-1-treated rats had decreased PLA2 activity, lavage phospholipid content, leak, weight gain, and lavage protein increases compared with rats given IL-1 intratracheally. Mepacrine treatment also decreased lung neutrophil accumulation, but not lung lavage cytokine-induced neutrophil chemoattractant (CINC) levels, in rats given IL-1 intratracheally. In parallel experiments, mepacrine treatment reduced the adhesion of human neutrophils to IL-1-treated human umbilical vein endothelial cells in vitro. Our results indicate that PLA2 activity participates in the lung neutrophil retention and pulmonary vascular leak that develops in rats given IL-1 intratracheally.
authors.affiliation: Webb-Waring Institute for Biomedical Research and the Department of Medicine at the University of Colorado Health Sciences Center, Denver, USA.
authors.forename: Y M
authors.initials: YM
authors.lastname: Lee
authors.forename: B M
authors.initials: BM
authors.lastname: Hybertson
authors.forename: L S
authors.initials: LS
authors.lastname: Terada
authors.forename: A J
authors.initials: AJ
authors.lastname: Repine
authors.forename: H G
authors.initials: HG
authors.lastname: Cho
authors.forename: J E
authors.initials: JE
authors.lastname: Repine
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006133:Growth Substances / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D011654:Pulmonary Edema / Q000503:physiopathology; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D004791:Enzyme Inhibitors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D010743:Phospholipids; D011506:Proteins; D009195:Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine