Background: Eosinophils contribute to the pathogenesis of asthma. They can be activated by extracellular nucleotides released following cell damage and inflammation. This study aimed at identifying the ATP-gated P2X receptor(s) present on eosinophils and determining their contribution to eosinophil biology. Methods: Human eosinophils were isolated from the peripheral blood of healthy and asthmatic volunteers. qPCR and Western blots were used to determine respectively eosinophil P2X receptor mRNA and protein expression level. Conventional whole cell patch-clamp experiments were performed to identify eosinophil functional P2X receptor subtypes. Eosinophil CD11b cell surface expression was measured by flow cytometry and cell adhesion was assessed as residual eosinophil peroxidase activity of adherent eosinophils as previously described by Zhu et al. (2000). Data are expressed as mean±SEM. For electrophysiology experiments, currents from at least 3 cells were averaged per donor. Student t-test was performed when Gaussian distribution was observed, otherwise the Wilcoxon matched-pairs and Mann-Whitney tests were used for paired and unpaired values respectively. CD11b flow cytometry experiment significance was assessed by the ratio paired t-test. Friedman test and Dunn’s multiple comparison test were used for the adhesion assays. Results: Transcripts for P2X1, P2X4 and P2X5 receptors were expressed in healthy and asthmatic eosinophils (n=6 for each). The P2X1 receptor agonist α,β-meATP (10 μM) evoked rapidly activating and desensitizing inward currents (peak 18±3 pA/pF at -60 mV, n=3) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 μM) (3±2 pA/pF, n=8, p=0.008). These currents were smaller in eosinophils from asthmatic patients (8±2 versus 27±5 pA/pF for healthy, n=12 and 13 respectively, p<0.001), but were rescued following treatment with a high concentration of the nucleotidase apyrase (17±5 pA/pF for 10 IU/ml and 11±3 pA/pF for 0.32 IU/ml, n=6 for both, p=0.031), indicating that the channels are partially desensitised by extracellular nucleotides. α,β-meATP (10 μM) increased active CD11b (from the integrin complex αMβ2) expression in eosinophils from healthy, but not asthmatic donors (143±21% and 108±11% of control response, n=13 and 10 respectively, p=0.041). Because αMβ2 integrin mediates eosinophil adhesion to ICAM-1 and BSA (Zhu et al., 2000), we investigated P2X1 receptor contribution to eosinophil adhesion on BSA-coated plates. α,β-meATP increased healthy (18±2% compared to control 10±1%, n=6, p=0.014) but not asthmatic eosinophil adhesion (13±1 compared to control 10±0%, n=6). NF449 (1μM) inhibited α,β-meATP-mediated healthy eosinophil adhesion (12±1%, n=6, p=0.0447), but had no effect on asthmatic eosinophil adherence properties (9±1%, n=6). Conclusion: Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil αMβ2 integrin-dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared to healthy eosinophils, probably due to higher basal release of nucleotide(s). This could be a mechanism for retention of eosinophils in a tissue compartment.