Platelet-activating factor-acetylhydrolase can monodeacylate and inactivate lipoteichoic acid.
Bacterial lipoteichoic acid (LTA) shares a structural motif with platelet-activating factor (PAF). Both molecules are strong inflammatory agents and have a glycerol backbone with two lipid chains at the sn-1 and sn-2 positions. PAF is normally inactivated by PAF-acetylhydrolase (PAF-AH), a phospholipase A2 (PLA2), which removes a short acyl group at the sn-2 position. To investigate whether PAF-AH can similarly degrade LTA, we studied the effects of porcine PLA2, bee venom PLA2, and recombinant human PAF-AH on pneumococcal LTA (PnLTA) and staphylococcal LTA (StLTA). After incubation with a porcine or bee venom PLA2, a large fraction of PnLTA lost 264 Da, which corresponds to the mass of the oleic acid group at the sn-2 position. After incubation with recombinant human PAF-AH, PnLTA lost 264 Da; the reduction did not occur when PAF-AH was exposed to Pefabloc SC, an irreversible inhibitor of the PAF-AH active site. Following PAF-AH treatment, PnLTA and StLTA were not able to stimulate mouse RAW 264.7 cells to produce tumor necrosis factor alpha but could stimulate CHO cells expressing human TLR2. This stimulation pattern has been observed with monoacyl PnLTA prepared by mild alkali hydrolysis (22). Taking these data together, we conclude that PAF-AH can remove one acyl chain at the sn-2 position of LTA and produce a monoacyl-LTA that is inactive against mouse cells.
Seo
Ho Seong
HS
Department of Pathology, University of Alabama at Birmingham, 845 19th St. South (BBRB 614), Birmingham, AL 35249-7331, USA.
Kim
Je Hak
JH
Nahm
Moon H
MH
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors / Q000502:physiology*; D000215:Acylation; D000818:Animals; D002460:Cell Line; D006358:Hot Temperature; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D054467:Phospholipases A2; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology; D013450:Sulfones / Q000494:pharmacology; D013682:Teichoic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008074:Lipoproteins; D015842:Serine Proteinase Inhibitors; D013450:Sulfones; D013682:Teichoic Acids; D015060:1,2-Dipalmitoylphosphatidylcholine; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; C009900:lipoteichoic acid; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase