Summary
The arachidonate lipoxygenase products 12-hydroxy-5, 8,10,14-eicosatetraenoic acid (12-HETE) and 5(S),12(R)-dihydroxy-6,8,10,14-eicosatetraenoic acid (leukotriene B4, LTB4) are potent leucocyte chemoattractants in vitro and in vivo. Both 12-HETE and LTB4-like material are found in increased amounts in lesional skin in psoriasis. Epicutaneous administration of 12(R,S)-HETE and LTB4 in normal skin evokes neutrophil and mononuclear dermal infiltrates accompanied by collections of neutrophils in the epidermis. Similar appearances result from the application of LTB4 to uninvolved skin in psoriasis. We have now investigated the effects of single and multiple epicutaneous applications of 12(R,S)-HETE and LTB4, both alone and in combination, in normal human skin and in clinically uninvolved skin of patients with psoriasis. As in the case of LTB4, erythematous responses to 12(R,S)-HETE were similar in normal skin and in psoriasis. Similar neutrophil polymorphonuclear responses were evoked by topical application of 50 ng LTB4 and 20 μg 12(R,S)-HETE. Application of the combination of 12(R,S)-HETE and LTB4 evoked only a partially additive erythematous response, and no evidence of an additive neutrophilotactic response was detected histologically. Multiple applications resulted in tolerance both clinically and histologically. Cross tolerance to 12(R,S)-HETE and LTB4 occurred in the majority of subjects. These results suggests that both 12(R,S)-HETE and LTB4 may be important in the production and control of the magnitude of the inflammatory events in psoriasis.
Similar content being viewed by others
References
Bhattacherjee P, Hammond B, Salmon JA, Stepney R, Eakins KE (1981) Chemotactic response to some arachidonic acid lipoxygenase products in the rabbit eye. Eur J Pharmacol 73:21–28
Brain SD, Camp R, Dowd PM, Kobza Black A, Woolard PM, Mallet AI, Greaves MW (1982) Psoriasis and leukotriene B4. Lancet II:762 (Letter)
Brain S, Camp R, Kobza Black A, Dowd PM, Greaves MW (1983) Biological activity due to arachidonic acid lipoxygenase products in psoriasis. J Invest Dermatol 80:360
Brain S, Camp R, Dowd PM, Kobza Black A, Wollard PM, Mallet AI, Greaves MW (1983) Release of leukotriene B4 (LTB4) and monohydroxy-eicosatetraenoic acids (HETEs) from the involved skin of patients with psoriasis. In: Piper PJ (ed) Leukotrienes and other lipooxygenase products. Research Studies Press, pp 248–258
Brain S, Camp R, Cunningham FM, Dowd PM, Kobza Black A, Greaves MW (1984) Leukotriene B4-like material in scale of psoriatic lesions. Br J Pharmacol 83:313
Burks JW, Montgomery H (1943) Histopathologic study of psoriasis. Arch Derm Syph 48:479
Camp R, Mallet AI, Woollard PM, Brain S, Kobza Black A, Greaves MW (1983) The identification of hydroxy fatty acids in psoriatic skin. Prostaglandins 26:421–447
Camp R, Coutts AA, Greaves MW, Kay AB, Walport MJ (1984) Responses of human skin to intradermal injections of leukotriences C4, D4 and B4. Br J Pharmacol 80:202
Camp R, Russell-Jones R, Brain S, Woollard P, Greaves MW (1984) Production of intraepidermal microabscesses by topical application of leukotriene B4. J Invest Dermatol 82:202
Carr SL, Higgs CA, Salmon JA, Spayne JA (1981) The effects of arachidonate lipoxygenase products on leukocyte migration in rabbit skin. Br J Pharmacol 73:106
Clark ER, Clark EL (1935) Observations on changes in blood vascular endothelium in the living animal. Am J Anat 57:385
Colditz IS, Movat HZ (1984) Chemotactic factor-specific desensitisation of skin to infiltration by polymorphonuclear leukocytes. Immunol Letts 8:83–87
Colditz IS, Movat HZ (1984) Desensitization of acute inflammatory lesions to chemotaxins and endotoxins. J Immunol 133:2163–2168
Dowd PM, Woollard PM, Kobza Black A, Camp R, Greaves MW (1983) The effect of intradermal infusions of 12-hydroxy-cicosatetraenoic acid (12-HETE) in normal human skin. Br J Dermatol 109:693–694 (Abstract)
Dowd PM, Kobza Black A, Woollard PM, Camp R, Greaves MW (1984) The in vivo properties of 12-hydroxy-eicosatetraenoic acid (12-HETE) in normal skin. J Invest Dermatol 82:412 (Abstract)
Dowd PM, Kobza Black A, Woollard PM, Camp R, Greaves MW (1985) Cutaneous responses to 12-hydroxy-5, 8,10,14-eicosatetraenoic acid (12-HETE). J Invest Dermatol 84:537–541
Ford-Hutchinson AW, Bray MA, Doig MV, Shipley ME, Smith MJH (1980) Leukotriene B4, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286:264–265
Goetzl EJ, Gorman RR (1977) Stimulation of human eosinophil polymorphonuclear leukocyte chemotaxis and random migration by 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid. J Clin Invest 59:179–183
Goetzl EJ, Gorman RR (1978) Chemotactic and chemokinetic stimulation of human eosinophil and neutrophil polymorphonuclear leukocytes by 12-L-hydroxy-5,8-heptadecatrienoic acid (HHT). J Immunol 120:526–531
Goetzl EJ, Valone FH, Reinhold VN, Gorman RR (1979) Specific inhibition of the polymorphonuclear leukocyte chemotactic response to hydroxy-fatty acid metabolites of arachidonic acids. Am J Pathol 104:55–62
Higgs GA, Salmon JA, Spayne JA (1981) The inflammatory effects of hydroperoxy and hydroxy acid products of arachidonate lipoxygenase in rabbit skin. Br J Pharmacol 74:429–433
Metchnikoff E (1893) Lectures on the comparative pathology of inflammation. Kegan Paul, Trench, Trubner, London
O'Flaherty JT, Thomas MJ, Lees CJ, McCall CE (1981) Neutrophil-aggregating activity of monohydroxy-eicosatetraenoic acids. Am J Pathol 104:55–62
Palmer RMJ, Stepney RJ, Higgs GA, Eakins KE (1980) Chemokinetic activity of arachidonic acid lipoxygenase products on leukocytes of different species. Prostaglandins 20:411–418
Soter NA, Lewis RA, Corey EJ, Austen KF (1983) Local effects of synthetic leukotrienes (LTC4, LTD4, LTE4 and LTB) in human skin. J Invest Dermatol 80:115–119
Turner SR, Tainer JA, Lynn WS (1975) Biogenesis of chemotactic molecules by the arachidonate lipoxygenase system of platelets. Nature 257:680–681
Wong E, Camp RD, Greaves MW (1985) The responses of normal and psoriatic skin to single and multiple topical applications of leukotriene B4. J Invest Dermatol 84:421–423
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dowd, P.M., Kobza Black, A., Woollard, P.W. et al. Cutaneous responses to 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and 5,12-dihydroxyeicosatetraenoic acid (leukotriene B4) in psoriasis and normal human skin. Arch Dermatol Res 279, 427–434 (1987). https://doi.org/10.1007/BF00412586
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00412586