Molecular basis of photocontact allergy

Abstract

SynopsisPhotocontact allergy, an acquired altered reactivity of the skin to light in the presence of a photosensitizer, has for many years been considered to be a delayed-type hypersensitivity. The response has been postulated as being mediated via the formation o f a protein-photoallergen conjugate acting as a complete antigen. The purpose of this paper is to bring together evidence at the molecular level which supports this theory of photoallergy.All photoallergens studied so far have been shown to be able to bind to proteins under the influence of ultraviolet light. Photoallergen-protein binding in most cases is non-specific; the exception, that of tetrachlorosalicylanilide (T4CS), displays a high specificity towards serum albumin.The mechanism of protein-photoallergen binding is thought to proceed via the formation of highly reactive species such as free radicals. Free radicals have now been observed using electron spin resonance spectroscopy for at least five photoallergens.Macrophage inhibition and lymphocyte transformation experiments have indicated that proteinphotoallergen conjugates act as complete antigens. Further evidence for this is provided by the observation that photoconjugates injected into guinea-pigs can induce a photoallergic response in the absence of irradiation. The response produced by T4CS-serum albumin conjugates is greater than that produced by any other combination of photoallergen and protein. The potency of the T4CS-serum albumin photoconjugate in inducing photoallergy, together with the binding specificity of T4CS, suggest that albumin may have a special role as a carrier protein in T,CS photoallergy. RCum6La base mol&ulaire de I'allergie par photocontact L'allergie par photocontact, une reaction de la peau a la lumitre en presence d'un photosensibilisateur, a ete, pendant de nombreuses annees, consideree comme une hypersensibilite retardee. Ce phenomtne semble se traduire par la formation d'un compose proteine/photoallergene agissant comme antigene. Le but de cet article est de demontrer I'evidence qui corrobore cette theorie de la photoallergie au niveau moleculaire.Tous les photoallergitnes etudies jusqu'alors se sont reveles aptes a retenir les prottines sous I'influence de la lumiere ultraviolette. Dans la plupart des cas, la retention de proteines photoallergtnes n'est pas specifique; il existe une exception cependant: celle du tetrachlorosalicylanilide (T4CS) qui presente une haute specificit6 envers le serum albumine. Le mecanisme de retention des proteines photoallergenes est sense se traduire par la formation d'especes hautement reactives telles que les radicaux libres. Les radicaux libres ont maintenant CtC observes a I'aide de spectroscopie a spin electronique pour environ cinq photoallergenes.Les experiences d'inhibition des macrophages et de transformation des lymphocytes ont montre que les proteines photoallergenes conjuguent leurs effets comme des antigenes a part entitre. Une autre evidence de ce phenomene est demontree par I'observation que des molCcules photocon...

Determination of quinacrine dihydrochloride dihydrate stability and characterization of its degradants

“…SI 4 is quite distinct from the other potential degradation products. The diaryl ketone group, which is limited to this particular impurity imparts photoallergenicity and phototoxicity 50. Additionally, an analogy with acetaminophen is noted and can confer hepatotoxicity 51,52…”

Photohaptenic Properties of Fluoroquinolones

“…A photohaptenic moiety is one of the salient properties of photoallergic chemicals. Upon exposure to UVA, protein is covalently coupled (23)(24)(25) and cells are easily conjugated (26,27) with a photohapten. We have shown that photoallergic sensitivity to a photohapten 3,3',4',5-tetrachlorosalicylanilide (TCSA) (reviewed by Tokura and Takigawa 28) and a photosensitive drug afloqualone (AQ) (29) is a T-cellmediated delayed-type hypersensitivity (DTH) reaction, in which photohapten conjugation of epidermal cells (EC) initiates immunologic consequences for sensitization and elicitation (29)(30)(31).…”

Immunotoxicology

“…Photoallergens would be expected to also be phototoxicants and this conclusion is supported by studies with known photoallergens (Bec et al, 1986;de Vries et al, 1990;Pendlington and Barratt, 1990;Tokura, 1998;Miranda et al, 1999;Lovell and Jones, 2000;Tokura, 2000). Thus, photoallergy is simply a special form of phototoxicity.…”