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

Abstract

Certain arachidonic 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 less than 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.

Is enhanced platelet activation the missing link leading to increased cardiovascular risk in psoriasis?

“…The increased platelet activation releases many inflammatory and mitogenic compounds which are being linked to the pathogenesis of psoriasis [32]. Severe psoriatic patients were found to have increased platelet CD62 expression, indicating a high prevalence of subclinical atherosclerosis in them [33].…”

Primary Hemostasis, Platelet Functions and Coagulation in Psoriasis

“…Literature data on platelet aggregation arc dis cordant but most studies are in favor of an increased aggregability [3.4] possibly due to abnormalities in arachidonic acid metabolism [5,6], To our knowledge, no previous report on platelet adhesivity is available. We demonstrate here a strong defect of this function in psoriasis.…”

Testing of Lipoxygenase Inhibitors, Cyclooxygenase Inhibitors, Drugs with Immunomodulating Properties and Some Reference Antipsoriatic Drugs in the Modified Mouse Tail Test, an Animal Model of Psoriasis

“…The negative role in the disease of LTB4 and 12-R-HETE was attributed to their che moattractant properties [2, 9] (LTB4 > 12-R-HETE) [6], the induction of increased DNA synthesis in human kératinocytes [3,4] and the influence on lymphocyte function (only LTB4) [5]. In vivo, after intradermal adminis tration, LTB4 and 12-R-HETE induced wheal and flare reactions, increase in vascular per meability, intraepidermal microabscesses and epidermal hyperproliferation [10], Although some of the characteristics of psoriasis are mimicked, none of both mediators is able to induce the disease as an entity.…”