Presentation: Increased expression of purinergic (P2Y12) receptor and cysteinyl leukotriene receptors in the lung tissue of a mouse model of allergic asthma ( World Allergy Congress)

Wednesday, 14 October 2015

Hall D1 Foyer (Floor 3) (Coex Convention Center)

Tu/Hoang Kim Trinh, MD , Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea

Duy Le Pham, MD , Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea

Jing-Nan Liu, MD , Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea

Hae-Sim Park, MD, PhD , Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea

Yoo Seob Shin, MD, PhD , Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea

Background and objectives: Cysteinyl leukotrienes C4, D4 and E4 mediate allergic inflammation by interacting with type 1 and 2 cysteinyl leukotriene receptors (CysLT1R, CysLT2R), G protein-coupled receptor (GPR) 99 and indirectly with purinergic receptor P2Y12 (P2Y12R). P2Y12R expressed on platelets and eosinophil granules are required for platelet activation, thus resulting in the recruitment of eosinophils in the lungs ^{(1), (2)}. To understand the role of these leukotriene related receptors in allergic asthma, we compared the expressions of CysLT1R, CysLT2R, GPR99 and P2Y12R in an Ovalbumin-induced allergic asthma mouse model.

Methods: BALB/c mice were injected intraperitoneally with ovalbumin (OVA) followed by nebulized OVA challenges, from which bronchoalveolar lavage fluid (BALF) cells and lung tissues were collected. Vehicle was treated as a control group. For platelet removal, mice were injected with anti-CD42b antibody. Western blot, immunocytochemistry and immunohistochemistry were applied to evaluate the expressions of these receptors.

Results: P2Y12R, CysLT1R and CysLT2R signals were distributed in epithelial lining and lung parenchyma of platelet-depleted and non-platelet-depleted mice, respectively. The expressions of P2Y12R, CysLT1R and CysLT2R were significantly higher in the lung tissue of OVA-sensitized mice than in vehicle-treated mice (P = 0.047; P= 0.04; P =0.045, respectively). The expression ratios of CysLT1R and CysLT2R to P2Y12R were 1.4 and 1.1 to 1 in vehicle-treated mice; 1.3 and 1.1 to 1, in OVA-sensitized mice. P2Y12R, CysLT1R and CysLT2R were localized to eosinophils from BALF and were elevated markedly after OVA challenges in OVA-sensitized mice, while GPR99 was found with the lowest level in BALF cells and lung tissue.

Conclusions: Increased expressions of P2Y12R, CysLT1R and CysLTR2 were noted in the lung tissue of a mouse model of allergic asthma. Additional effects of P2Y12R antagonists on CysLTR1 antagonists should be investigated as a future therapeutic target.

Key Words: P2Y12R antagonist, CysLTR1, CysLTR2, eosinophil

(1) S.C. Pitchford, Blood, 105 (2005), pp. 2074–2081

(2) Cummings H.E, J Immunol, 2013; 191(12), 10.4049/jimmunol.1302187

1060 Increased expression of purinergic (P2Y12) receptor and cysteinyl leukotriene receptors in the lung tissue of a mouse model of allergic asthma