The platelet P2 receptors in inflammation

Summary

In addition to their well characterized and established role in haemostasis and thrombosis, platelets contribute to the pathogenesis of inflammation. Adenine nucleotides are signalling molecules that regulate the function of virtually every cell in the body, by interacting with P2 receptors. Their important role in inflammation is well established. In the last few years, the pro-inflammatory roles of adenine nucleotides interacting with their platelet P2 receptors has emerged. In particular, it was shown that the platelet P2Y₁₂ receptor for ADP significantly contributed to the proinflammatory effects of cysteinyl leukotrienes (CysLT) in experimental models of asthma in mice. More importantly, it was recently shown that P2Y₁₂ variants were associated with lung function in a large family-based asthma cohort and that the P2Y₁₂ antagonist prasugrel tended to decrease bronchial hyper-reactivity to mannitol in patients with allergic bronchial asthma in a randomized, placebo controlled trial.

Conclusion

These data strongly suggest that P2Y₁₂ may represent an important pharmacological target for the treatment of patients with allergic bronchial asthma.

Zusammenfassung

Neben ihrer gut beschriebenen und etablierten Rolle bei Hämostase und Thrombose tragen die Thrombozyten auch zur Pathogenese von Entzündungen bei. Adenin-Nukleotide sind Signalmoleküle, die über die Interaktion mit P2-Rezeptoren die Funktion praktisch aller Körperzellen regulieren. Ihre wichtige Rolle bei Entzündungen ist gut belegt. In den letzten Jahren wurden die pro-inflammatorischen Wirkungen für Adenin-Nukleotide, die mit Plättchen-P2-Rezeptoren interagieren, beschrieben. Insbesondere wurde gezeigt, dass der Plättchen-P2Y₁₂-Rezeptor für ADP in experimentellen Asthmamodellen bei Mäusen maßgeblich zu den pro-inflammatorischen Wirkungen der Cysteinyl-Leukotriene (CysLT) beiträgt. Darüber hinaus wurde kürzlich nachgewiesen, dass P2Y₁₂-Varianten in einer großen, familienbasierten Asthma-Kohorte mit der Lungenfunktion assoziiert waren und dass der P2Y₁₂-Antagonist Prasugrel in einer randomisierten, Placebo-kontrollierten Studie die bronchiale Hyperreaktivität gegen Mannitol bei Patienten mit allergischem Bronchialasthma tendenziell verringerte.

Schlussfolgerung

Diese Daten liefern starke Anhaltspunkte dafür, dass P2Y₁₂ ein wichtiges pharmakologisches Ziel für die Behandlung von Patienten mit allergischem Bronchialasthma darstellen könnte.

Keywords

P2Y12 - asthma - inflammation - platelets - cysteinyl leukotriens

Schlüsselwörter

P2Y12 - Asthma - Entzündung - Plättchen - Cysteinyl-Leukotriene

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