title: Influence of sphingomyelin and TNF-alpha release on lethality and local inflammatory reaction induced by Loxosceles gaucho spider venom in mice.
abstract: It is well known that Loxosceles venom induces local dermonecrosis in rabbits, guinea pigs and humans but not in mice, although, depending on the dose, Loxosceles venom can be lethal to mice. In this work we demonstrate that mice injected intradermally in the dorsal area of the back can survive a lethal dose of Loxosceles gaucho venom and also develop an inflammatory reaction (with infiltration of leukocytes shown by histological analysis) at the local injection site when the venom is co-administered with sphingomyelin. It was observed that more venom was retained for a longer period of time at the local injection site when venom was co-administered with sphingomyelin. The presence of exogenous sphingomyelin did not influence significantly the release of TNF-alpha induced by L. gaucho venom. These results suggest that the action of venom on sphingomyelin, producing ceramide phosphate, causes the development of an inflammatory reaction, which in turn traps the venom in the local area for a long period of time and does not allow it to disperse systemically in a dose sufficient to cause death. Our findings also indicate that the size and availability of the local sphingomyelin pool may be important in determining the outcome of Loxosceles envenoming in different mammalian species.
authors.affiliation: St George's Medical School, Division of Infectious Diseases, Cranmer Terrace, London SW 17 ORE, UK. martadomingos@uol.com.br
authors.forename: M O
authors.initials: MO
authors.lastname: Domingos
authors.forename: K C
authors.initials: KC
authors.lastname: Barbaro
authors.forename: W
authors.initials: W
authors.lastname: Tynan
authors.forename: J
authors.initials: J
authors.lastname: Penny
authors.forename: D J M
authors.initials: DJ
authors.lastname: Lewis
authors.forename: R R C
authors.initials: RR
authors.lastname: New
mesh_terms: D000818:Animals; D002518:Ceramides / Q000008:administration & dosage / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000139:chemically induced*; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010727:Phosphoric Diester Hydrolases / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D013109:Sphingomyelins / Q000008:administration & dosage / Q000378:metabolism*; D013111:Spider Venoms / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D013112:Spiders / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D002518:Ceramides; D008081:Liposomes; D013109:Sphingomyelins; D013111:Spider Venoms; D014409:Tumor Necrosis Factor-alpha; C065576:ceramide 1-phosphate; C055161:loxosceles venom; D010727:Phosphoric Diester Hydrolases