Induction of Photoallergy in Guinea-Pigs by Injection of Photoallergen-Protein Conjugates

Barratt, Martin D.; Goodwin, Benjamin; Lovell, W.W.

doi:10.1159/000234454

Cited by 14 publications

(2 citation statements)

References 12 publications

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“…Recent in vivo evidence for the importance of protein-photoallergen conjugates has been generated in this laboratory [31]. From consideration of the work by Herman and Sams [30], together with the high binding affinity shown by T4CS towards serum albumin, it was argued that a photoallergic response to T4CS ought to be induced in guinea-pigs by injection of T4CS-guinea-pig albumin photoconjugate (as opposed to the conventional induction route of topical application of T4CS followed by ultraviolet irradiation).…”

Section: Biological Evidence For the Role Of Photoconjugates In Photomentioning

confidence: 99%

Molecular basis of photocontact allergy

Pendlington

Barratt

1990

Intern J of Cosmetic Sci

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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...

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Section: Biological Evidence For the Role Of Photoconjugates In Photomentioning

confidence: 99%

Molecular basis of photocontact allergy

Pendlington

Barratt

1990

Intern J of Cosmetic Sci

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“…Photoallergy resembles contact hypersensitivity; the only difference is that the drug requires activation by light, instead of, for example, enzymes, in order to provoke this unwanted immune response . The photoexcited drug or its reactive photoproduct, called hapten, irreversibly binds to proteins, resulting in the formation of an antigen; this is supposed to be the initial step in photoallergy . Subsequently, the antigen triggers immunologic reactions that eventually result in the symptoms of contact hypersensitivity, in this case, photoallergy , .…”

Section: Introductionmentioning

confidence: 99%

Photoaddition of Fluphenazine to Nucleophiles in Peptides and Proteins. Possible Cause of Immune Side Effects

Caffieri

Miolo

Seraglia

et al. 2007

Chem. Res. Toxicol.

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By the action of UVA light, fluphenazine reacted with nucleophiles through a mechanism involving defluorination of its trifluoromethyl group, giving rise to carboxylic acid derivatives that were easily detected by electrospray mass spectrometry. This photoreaction took place with alcohols, sulphydryls, and amines. When irradiation of fluphenazine was carried out in the presence of an amino acid at pH 7.4, the alpha-amino group was covalently bound to the drug. With amino acids possessing a further nucleophilic residue on the side chain, such as lysine, tyrosine, and cysteine--but not serine--both groups reacted, resulting in a fluphenazine-amino acid-fluphenazine diadduct. The same occurred with the physiological peptide glutathione (gamma-glutamylcysteinylglycine). By means of MALDI mass spectrometry, it was shown that fluphenazine also covalently bound to peptides and proteins such as calmodulin. This binding may result in the formation of antibodies, ultimately leading to the destruction of the granulocytes and thus suggesting that photoactivation of this drug may play a role in its clinical side effects, such as agranulocytosis.

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Cutaneous Photosensitization: Hazard and Regulation

Johnson

1991

Photobiology

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Induction of Photoallergy in Guinea-Pigs by Injection of Photoallergen-Protein Conjugates

Cited by 14 publications

References 12 publications

Molecular basis of photocontact allergy

Molecular basis of photocontact allergy

Photoaddition of Fluphenazine to Nucleophiles in Peptides and Proteins. Possible Cause of Immune Side Effects

Cutaneous Photosensitization: Hazard and Regulation

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