IgE Receptor-Mediated Histamine Release in Human Lung Mast Cells: Modulation by Purinergic Receptor Ligands.

BACKGROUND: Mast cells derived from human lungs (HLMCs) express multiple G-protein coupled purinergic receptors (P2YR) and the so-called α-ketoglutarate receptor GPR99, which is homologous to P2YR. The role of the P2YR of HLMC is not clear. Thus, the aim of the present study was to determine the effects of purinergic and purine-related compounds on allergic histamine release (HR) in HLMCs.

METHODS: FcεRI-mediated HR was quantified in primary culture of HLMC (cHLMC). The effects of the FcεRI-mediated allergic stimulation on the expression of GPR99 were also determined.

RESULTS: Adenosine produced a dual effect on HR: enhancement and marked inhibition at low and high concentrations, respectively. Adenosine 5'-monophosphate (AMP) did not affect FcεRI-mediated HR. However, the non-hydrolysable AMP analog, adenosine-5'-O-thiomonophosphate (AMP-S), concentration dependently inhibited the FcεRI-mediated HR without any enhancement. At high concentrations, α-ketoglutarate moderately inhibited FcεRI-mediated HR. However, inhibitions by AMP-S and α-ketoglutarate of HR were dissimilar in the inhibitory manner (IC50 and Hill slope) on histamine release by allergic stimulation.

CONCLUSIONS: cHLMC express functional GPR99 receptor that is up-regulated following allergic stimulation. Responsiveness to AMP-S is the first indication that cHLMC express P2YR, the activation of which can inhibit FcεRI-mediated HR.