Platelet Activation, P-Selectin, and Eosinophil β1-Integrin Activation in Asthma

Rationale: Eosinophil beta(1)-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma. Objectives: Determine the relationships between beta(1)-integrin activation and pulmonary function or eosinophil-bound P-selectin in subjects with asthma of varying severity and discern the source of eosinophil-bound P-selectin. Methods: Blood was assayed by flow cytometry for P-selectin and activated beta(1)-integrin on eosinophils and platelets. Plasma was analyzed with ELISA for soluble P-selectin, platelet factor 4, and thrombospondin-1. Measurements and Main Results: Activated beta(1)-integrin correlated with eosinophil-bound P-selectin among all subjects with asthma even though activated beta(1)-integrin was higher in subjects with nonsevere asthma than severe asthma. Activated beta(1)-integrin correlated inversely with FEV1 corrected for FVC only in younger subjects with nonsevere asthma. Paradoxically, platelet surface P-selectin, a platelet activation marker, was low in subjects with severe asthma, whereas plasma platelet factor 4, a second platelet activation marker, was high. Correlations indicated that P-selectin-positive platelets complexed to eosinophils are the major source of the eosinophil-bound P-selectin associated with beta(1)-integrin activation. After whole-lung antigen challenge of subjects with nonsevere asthma, a model of asthma exacerbation known to cause platelet activation, circulating eosinophils bearing P-selectin and activated beta(1)-integrin disappeared. Conclusions: The relationship between eosinophil beta(1)-integrin activation and pulmonary function was replicated only for younger subjects with nonsevere asthma. However, we infer that platelet activation and binding of activated platelets to eosinophils followed by P-selectin-mediated eosinophil beta(1)-integrin activation occur in both nonsevere and severe asthma with rapid movement of platelet-eosinophil complexes into the lung in more severe disease.