Isolation, Biological and Antigenic Properties of a Specific Toxin Formed in Thermally Altered Mouse Skin

Abstract

Abstract. A lipid‐protein complex, which has a lethal effect on recipient animals, was isolated from mouse skin exposed to controlled thermal energy. A new isolation procedure was developed, which takes advantage of the toxic activity present in thermally modified skin, to trace the fate of the active compound. A bioassay was designed for this purpose by injecting Thorotrast into the recipient animals. The toxic lipid‐protein complex and the corresponding derivative from native skin were shown to have the same lipid (40%) and protein (60%) content. The lipid moieties of both derivatives were made up of six different lipid classes. The toxic compound differed from the non‐toxic material only by its larger size and higher density. Equivalent results were obtained on samples isolated, after the removal of surface lipids and soluble cell constituents, from the donor skins prior to the application of thermal energy i.e. processing “skin residues”. The biological activity was shown to reside in the apoprotein while the lipid moiety contributes to the toxic activity to a certain extent. The results suggest that the toxic compound is a polymeric form produced by thermal energy from a naturally occurring precursor. The toxin has a specific antigenic property protecting mice after active and passive immunotherapy against a lethal bum injury in vivo. This suggests strongly that the toxic compound is an etiological factor responsible for the high mortality after severe burns. It is significant that, if scalding was applied to the same extent as the dry heat burns in vivo, the injured animals survived. This was interpreted to support the hypothesis of a specific mechanism being responsible for toxin formation. The experimental results suggest that a specific therapy for the “late mortality” after severe human burns might be possible.

Specific impairment of host defense for pseudomonas infection in mice by a burn toxin derived from thermally altered human skin

“…was tolerated by the animals without symptoms. The nontoxic precursor derived froni unburned skin was not toxic to any degree for RES-blocked mice [15,17]. Also, the antitoxie IgG fractions used were found to protect mice from o t h e r w i s e l e t h a l b u r n s in vivo [17].…”

“…Specific burn toxins produced in thermally exposed mouse and human skin were shown previously [10,15,17,3] to produce 100~o mortality after i.p. injections of 0.35 mg/g of body weight in RES-blocked mice.…”

“…Two burn toxins, one from human and one from mouse skin were produced by the standardized in vitro application of heat as described elsewhere [15]. The source for human burn toxin was skin split into layers 1 mm thick [10].…”

“…Thus, it became possible to mimic a given burn injury experimentally by injecting mouse/human toxin in sublethal doses in animals and to investigate the influence of a pseudomonas infection on mortality. At the same time, the possible protective effects of a resulting antitoxie IgG could be studied while avoiding the stress incurred by producing an actual burn wound [15,17].…”

Formation of a Specific ‘Burn Toxin’ in Mouse Skin by Thermal Injuries

“…By showing a clear quantitative correlation between the mortality rate and the extent of the skin injured in vivo by the same thermal exposure as applied to the skins in vitro, the production of a similar compound after burn injuries in living animals was suggested as compared with the experi mental model [13], i.e. the burn toxin must be assumed to have been formed.…”