Brief communication: MRGPRX2, atopic dermatitis and red man syndrome

Abstract

Vancoymycin causes red man syndrome, an itchy erythematous eruption involving the face, neck and upper torso. Atopic dermatitis also manifests itch and erythema, and staphylococcus δ-toxin contributes to this process. The antibiotic and toxin each provoke mast cell degranulation but the mechanism had not been understood. We have determined that these compounds evoke degranulation via interaction with the same receptor, MRGPRX2, on mast cells. A receptor antagonist inhibits this process. Antagonists of this receptor may have therapeutic potential.

Figure 1

Staphylococcus δ-toxin and vancomycin activate human MRGPRX2 to induce mast cell degranulation. A, The interaction of staphylococcus δ-toxin and vancomycin with a HEK-293 cell line stably expressing MRGPRX2. Intracellular calcium [Ca²⁺]i was determined by ratiometric Fura-2 imaging as an indicator of receptor activation after addition of staphylococcus δ-toxin (10 μM) and vancomycin (100 μM). The MRGPRX2 antagonist QWF was used at equal concentrations of the ligands. The traces represent responses in individual cells. B and C, Staphylococcus δ-toxin (10 μM) and vancomycin (100 μM) induce mast cell degranulation in the human LAD2 mast cell line. The level of mast cell degranulation was assessed by the release of β-hexosaminidase in mast cell granules, quantified by the level of its substrate p-nitrophenyl N-acetyl-β-d-glucosamide digested in a colorimetric assay,. QWF significantly decreases the mast cell degranulation induced by staphylococcus δ-toxin (P=0.0022) and vancomycin (P=0.0003). ** P≤0.01; ***P≤0.001.

Figure 2

Interaction of teicoplanin with human MRGPRX2 and mast cells. A, Teicoplanin does not activate human MRGPRX2 stably expressed in HEK-293 cells. Intracellular calcium [Ca²⁺]i was determined by ratiometric Fura-2 imaging as an indicator of receptor activation after addition of teicoplanin (100 μM). Each trace represents a unique cell. B, Teicoplanin does not induce degranulation in the human LAD2 mast cell line (P>0.05). NS indicates nonsignificant.