title: Apolipoprotein A-I diminishes acute lung injury and sepsis in mice induced by lipoteichoic acid.
abstract: Lipoteichoic acid (LTA), as a primary immunostimulus, triggers the systematic inflammatory responses. Our hypothesis is that ApoA-I can neutralize LTA toxicity, like its effect on LPS. BALB/c mice were challenged with LTA, followed by human ApoA-I administration. We found that ApoA-I could attenuate LTA-induced acute lung injury and inflammation and significantly inhibit LTA-induced IL-1beta and TNF-alpha accumulation in the serum (P<0.01 and P<0.05, respectively), as well as in bronchoalveolar lavage (BAL) fluid (P<0.01 and P<0.05, respectively). Moreover, ApoA-I could significantly reduce the L-929 cell mortality caused by LTA-activated macrophages in a dose-dependent fashion. Furthermore, ApoA-I treatment could diminish LTA-mediated NFkappaB nuclear translocation in macrophages. An in vitro binding assay indicated that ApoA-I can bind LTA. These results clearly indicated that ApoA-I can effectively protect against LTA-induced sepsis and acute lung damage. The mechanism might be related to the binding and neutralization of LTA.
authors.affiliation: Department of Biochemistry, School of Pharmacy, Fudan University, P.O. Box 257, No. 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Jiao
authors.forename: Man-Ping
authors.initials: MP
authors.lastname: Wu
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000145:classification / Q000302:isolation & purification / Q000627:therapeutic use*; D002460:Cell Line; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D018805:Sepsis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013682:Teichoic Acids / Q000633:toxicity*
chemical_list: D016632:Apolipoprotein A-I; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid