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Effects of Rupatadine on Platelet- Activating Factor–Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study)

Munoz-Cano R1,2, Ainsua-Enrich E3, Torres-Atencio I4, Martin M3, Sánchez-Lopez J1,2, Bartra J1,2, Picado C1,2,5, Mullol J2,5,6*, Valero A1,2,5*

1Unitat d’Al·lèrgia, Servei de Pneumologia i Al·lèrgia Respiratòria, Hospital Clínic and Universitat de Barcelona, Barcelona, Catalonia, Spain
2Immunoal·lèrgia Respiratòria Clínica i Experimental, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
3Biochemistry Unit, School of Medicine, Universitat de Barcelona, Barcelona, Catalonia, Spain
4Pharmacology Department, School of Medicine, Universidad de Panamá, Panamá
5Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Catalonia, Spain
6Unitat de Rinologia i Clínica de l’Olfacte, Servei d’Oto-rino-laringologia, Hospital Clínic and Universitat de Barcelona, Barcelona, Catalonia, Spain
*Both authors had similar senior responsibilities

J Investig Allergol Clin Immunol 2017; Vol 27(3) : 161-168
doi: 10.18176/jiaci.0117

Background: Platelet-activating factor (PAF) is a lipid mediator involved in the pathophysiology of several allergic diseases, for example, in the amplification of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with a demonstrated anti-PAF effect, although its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated.
Objectives: To compare the ability of rupatadine to inhibit PAF-induced MC degranulation with that of desloratadine and levocetirizine and to confirm the dual anti-H1 and anti-PAF activity of rupatadine.
Methods: The human MC line LAD2 and primary MCs (human lung tissue MCs [hLMCs]) were used. MC mediator release was evaluated using the b-hexosaminidase and histamine release assay. The effects of rupatadine (H1 antagonist + PAF receptor antagonist), desloratadine, and levocetirizine (H1 antagonists) on LAD2 and hLMCs were compared. The PAF receptor antagonists WEB2086, BN52021, and CV6209 were also tested. PAF receptor protein expression was evaluated in both LAD2 and hLMCs.
Results: CV6209 and rupatadine inhibited PAF-induced MC degranulation in both LAD2 and hLMCs. In LAD2, rupatadine (5 and 10 µM) and levocetirizine (5 µM), but not desloratadine, inhibited PAF-induced b-hexosaminidase release. Rupatadine (1-10 µM), levocetirizine (1-10 µM), and desloratadine (10 µM) inhibited PAF-induced histamine release. Rupatadine at 10 µM had an inhibitory effect on hLMC degranulation, but levocetirizine and desloratadine did not.
Conclusions: This study shows that rupatadine and, to a lesser extent, levocetirizine, but not desloratadine, inhibit PAF-induced degranulation in both LAD2 and hLMCs. These findings support the dual antihistamine and anti-PAF effect of rupatadine in allergic disorders.

Key words: CV6209, Desloratadine, LAD2, Levocetirizine, Mast cell, Platelet-activating factor, Rupatadine.