Cellular Mechanisms in Allergic Contact Dermatitis

Contact Allergy to Resin Acid Hydroperoxides. Hapten Binding via Free Radicals and Epoxides

“…In a previous study of 15-DAP, animals sensitized to this peroxide also reacted to 15-HPA (10). 15-HPDA cannot react via an epoxide, and animals sensitized to 15-HPDA did not cross-react significantly with /3-epoxyabietate. The cross-reactivity pattern between 15-HPA and the epoxides can be explained by another mechanistic route.…”

“…However, the two keto compounds that would form from 15-HPA and 15-HPDA would react with electron-rich sites in protein (NHZ and SH groups), generating two different antigens not likely to cross-react. 15-HPA would yield an ,ß-yfidiunsaturated ketone with which skin protein would react in a nucleophilic addition at C7, whereas 15-HPDA would yield a methyl phenyl type ketone on which a nucleophilic attack from protein would occur on the carbonyl group (31). The two antigens formed would have large structural differences and are not likely to cross-react since crossreactivity requires structural resemblance (15).…”

“…15-HPA would yield an ,ß-yfidiunsaturated ketone with which skin protein would react in a nucleophilic addition at C7, whereas 15-HPDA would yield a methyl phenyl type ketone on which a nucleophilic attack from protein would occur on the carbonyl group (31). The two antigens formed would have large structural differences and are not likely to cross-react since crossreactivity requires structural resemblance (15). The observed cross-reactivity in our study is therefore better explained by a direct radical coupling to proteins.…”

“…groups present in skin proteins and thereby induce contact allergy (14). In contact allergy, i.e., delayed type hypersensitivity, the allergens are low-molecular-weight compounds (haptens) bound covalently to endogenous proteins in the skin (15). The binding to protein is pivotal both at the first contact with the allergen (the sensitization phase) as well as at the subsequent contacts (the elicitation phase).…”

“…The binding to protein is pivotal both at the first contact with the allergen (the sensitization phase) as well as at the subsequent contacts (the elicitation phase). Cross-reactivity between different haptens can take place when the haptens form complete antigens that have identical or very similar epitopes which make them react with the same T-lymphocytes (15). Epoxides of abietic acid are interesting from a mechanistic point of view since it is possible that the hydroperoxide 15-HPA could yield an epoxide in the 13,14-position before it reacts to form the complete antigen (16)(17)(18)(19).…”