This project is designed to study humoral and cellular mediators which may be involved in the production of tissue damage in cutaneous photosensitivity. Uroporphyrin (URO) and demethylchlortetracycline (DMCT) will be used as prototypes of endogenous and exogenous phototoxic substances, respectively. General Electric F40BL tubes will be used as the source of UVA and 400-410 nm radiation, while Westinghouse FS40 tubes will be the source of UVB radiation.
The specific aims are: 1) to explore the mechanism(s) of complement activation induced by phototoxic chemicals and light. The participation of immunoglobulin will be investigated by using agammaglobulinemic sera; the role of kini system will be investigated by using protease-inhibitor-treated sera, and plasminogen depleted sera. Pathway of complement activation will be studied using EDTA-treated sera, EDTA-Mg-treated sera, or sera congenitally deficient in C4. Interaction of prototype phototoxic compounds with individual complement component will be investigated using purified complement components. After exposure to phototoxic chemicals and irradiation, alterations in primary structure and functional activity of the component will be evaluated. Role of singlet oxygen and peroxides in this interaction will be investigated using oxygen and peroxide scavengers. 2) To investigate the effect of phototoxic chemicals and light on the function of selected cells normally present in the dermis, namely, endothelial cells and mast cells. URO or OMCT will be added to capillary endothelial cells culture, in the presence or absence of: the appropriate radiation and/or complement, and/or polymorphonuclear cells (PMNS). Cell damage will be assessed by 51Chromium-release assay. Similar experiments will be performed using rat peritoneal mast cells, and histamine release will be assayed by enzymatic assay. 3) To study in an animal model in vivo whether the in vitro findings have relevance to tissue damage in phototoxic reactions. URO of DMCT will be injected intradermally to backs of albino guinea pigs, followed by the appropriate irradiation. Clinical and histologic changes will be evaluated by using C4-deficient guinea pigs, and guinea pigs deplet of C3 and C5 by cobra venom factor treatment. Role of PMNS will be studied in guinea pigs rendered neutropenic by enclophosphamide.
| Lim, H W (1989) Mechanisms of phototoxicity in porphyria cutanea tarda and erythropoietic protoporphyria. Immunol Ser 46:671-85 |
| Kerdel, F A; Soter, N A; Lim, H W (1987) In vivo mediator release and degranulation of mast cells in hematoporphyrin derivative-induced phototoxicity in mice. J Invest Dermatol 88:277-80 |
| Lim, H W; Hagan, M; Gigli, I (1986) Phototoxicity induced by hematoporphyrin derivative in C5-deficient, mast cell-deficient and leukopenic mice. Photochem Photobiol 44:175-80 |
| Lim, H W; Young, L; Hagan, M et al. (1985) Delayed phase of hematoporphyrin-induced phototoxicity: modulation by complement, leukocytes, and antihistamines. J Invest Dermatol 84:114-7 |
| Lim, H W; Kamide, R; Gigli, I (1985) Effect of captopril on the vascular permeability changes induced by C5a, histamine and compound 48/80. Br J Dermatol 112:43-51 |
