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Increased aggregation and arachidonic acid transformation by psoriatic platelets: evidence that platelet-derived 12-hydroxy-eicosatetraenoic acid increases keratinocyte DNA synthesis in vitro

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Summary

Certain archidonic metabolites may play a pathogenic role in psoriasis. Platelets are rich sources of 12-hydroxy-eicosatetraenoic acid (12-HETE) and thromboxane A2, mediators of skin inflammation and platelet aggregation, respectively. We have studied untreated psoriatic patients without a history of diabetes mellitus and smoking. In psoriatics, platelet aggregation elicited by thrombin, ADP, and ristocetin was significantly enhanced as compared with healthy adult volunteers. Enhancement of platelet aggregation was detected in patients with both minimal and widespread disease. The formation of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), a cyclooxygenase product, and 12-HETE, a 12-lipoxygenase product, was increased in psoriatics with widespread disease but not in those with minimal disease. Formation of 12-HETE was stimulated to a higher degree (125%) than HHT (98%) in psoriasis (P<0.05). Addition of platelet-derived 12-HETE to cultured human epidermal keratinocytes resulted in a stimulation of the DNA synthesis (68% at 10-7 M). These data suggest that platelet activation occurs in psoriasis, and that release of inflammatory and mitogenic compounds by activated platelets may play a role in the pathophysiology of psoriasis. Whether enhanced platelet aggregation in psoriasis is associated with occlusive vascular disease needs further investigation.

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References

  1. Berrettini M, Parise P, Costantini V, Grasselli S, Nenci GG (1985) Platelet activation in psoriasis. Thromb Haemost 53:195–197

    Google Scholar 

  2. Borgeat P, Samuelsson B (1979) Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci USA 76:2148–2151

    Google Scholar 

  3. Braverman IM (1972) Electron microscopic studies of the microcirculation in psoriasis. J Invest Dermatol 59:91–98

    Google Scholar 

  4. Chang W-C, Fukuda S, Tai H-H (1983) Cigarette smoking stimulates lipoxygenase but not cyclooxygenase pathway in platelets. Biochim Biophys Acta 115:499–505

    Google Scholar 

  5. Davi G, Reni GB, Averna M, Novo S, DiFede, Mattina A, Notarbartolo A, Strano A (1982) Enhanced platelet release reaction in insulin-dependent and insulin-independent diabetic patients. Haemostasis 12:275–281

    Google Scholar 

  6. Dowd PM, Kobza Black A, Woollard PM, Camp RDR, Greaves MW (1985) Cutaneous responses to 12-hydroxy-5,8,10,14-eicosatetraenoic acid. J Invest Dermatol 84:537–541

    Google Scholar 

  7. Goetzl EJ, Woods JM, Gorman RR (1977) Stimulation of human eosinophil and neutrophil polymorphonuclear leukocyte chemotaxis and random migration by 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid. J Clin Invest 59: 179–183

    Google Scholar 

  8. Hamberg M, Svensson J, Samuelsson B (1975) A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci USA 72:2994–2998

    Google Scholar 

  9. Hamberg M, Svensson J, Samuelsson B (1976) Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins. Proc Natl Acad Sci USA 71:3824–3828

    Google Scholar 

  10. Hammarström S, Hamberg M, Samuelsson B, Duell EA, Stawiski M, Voorhees JJ (1975) Increased concentrations of free arachidonic acid, prostaglandin E2 and F2 and of 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) in epidermis of psoriasis: evidence of perturbed regulation of arachidonic acid levels in psoriasis. Proc Natl Acad Sci USA 72:5130–5134

    Google Scholar 

  11. Hammarström S, Lindgren JA, Marcelo CL, Duell EA, Anderson TF, Voorhees J (1979) Arachidonic acid transformations in normal and psoriatic skin. J Invest Dermatol 73:180–183

    Google Scholar 

  12. Kragballe K, Voorhees JJ (1983) Arachidonic acid and leukotrienes in dermatology. J Invest Dermatol 81:293–296

    Google Scholar 

  13. Kragballe K, Desjarlais L, Marcelo CL (1985) Increased DNA synthesis of uninvolved psoriatic epidermis is maintained in vitro. Br J Dermatol 112:263–270

    Google Scholar 

  14. Kragballe K, Desjarlais L, Voorhees JJ (1985) Leukotrienes B4, C4, and D4 stimulate DNA synthesis of cultured human epidermal keratinocytes. Br J Dermatol 113:43–52

    Google Scholar 

  15. Kragballe K, Desjarlais L, Altman DA, Voorhees JJ (1986) Uninvolved psoriatic epidermis has increased capacity to synthesize 12-hydroxy-eicosatetraenoic acid. J Invest Dermatol 87:47–52

    Google Scholar 

  16. Levine PH (1973) An acute effect of cigarette smoking on platelet function. A possible link between smoking and arterial thrombosis. Circulation 48:619–623

    Google Scholar 

  17. Luderer JR, Riley DL, Demers LM (1983) Rapid extraction of arachidonic acid metabolites utilizing octadecyl reversephase columns. J Chromatogr 273:402–409

    Google Scholar 

  18. Marcelo CL, Kim YG, Kaine JL, Voorhees JJ (1978) Stratification, specialization, and proliferation of primary keratinocyte cultures. J Cell Biol 79:356–370

    Google Scholar 

  19. McDonald CJ, Calabresi P (1978) Psoriasis and occlusive vascular disease. Br J Dermatol 99:469–475

    Google Scholar 

  20. Ross R (1981) Platelet-derived growth factor. In: Baserga R (ed) Handbook of experimental pharmacology, vol 57. Springer, New York Heidelberg, pp 133–159

    Google Scholar 

  21. Saurs AR, Sprecher H, Saukarappa SK, Needleman P (1982) Selective inhibitors of platelet arachidonic acid metabolism: independent of lipoxygenase. In: Samuelsson B, Paoletti R (eds) Leukotrienes and other lipoxygenase products, vol 9, Raven, New York, pp 19–28

    Google Scholar 

  22. Walker JR, Littlewood SM, Dawson W, Allen BR (1983) Metabolism of (1-14C) arachidonic acid by peripheral blood cells from psoriatic patients. J Invest Dermatol 80:359

    Google Scholar 

  23. Wolf R, Machtey I, Feuerman EJ, Creter D (1981) Blood hyperviscosity in psoriasis. Acta Derm Venereol (Stockh) 61:153–154

    Google Scholar 

  24. Woollard PM (1985) Stereochemical difference between 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) in platelets and psoriatic lesions. J Invest Dermatol 84:455

    Google Scholar 

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Kragballe, K., Fallon, J.D. Increased aggregation and arachidonic acid transformation by psoriatic platelets: evidence that platelet-derived 12-hydroxy-eicosatetraenoic acid increases keratinocyte DNA synthesis in vitro. Arch Dermatol Res 278, 449–453 (1986). https://doi.org/10.1007/BF00455162

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