Activation of beta1 integrins on blood eosinophils by P-selectin.

ABSTRACT: Activation of ?(1) integrins of blood eosinophils, assessed by mAb N29, correlates inversely with FEV(1) in two paradigms for studying control of human asthma. We asked whether P-selectin causes eosinophil ?(1) integrin activation and results in increased adhesivity. By dual-label flow cytometry, eosinophils with high levels of surface-associated P-selectin had higher reactivity with the activation-sensitive anti-?(1) mAbs N29, 8E3, and 9EG7 than eosinophils with no or with a low-level of surface-associated P-selectin. Among patients with nonsevere asthma, surface P-selectin correlated with N29, 8E3, and 9EG7 signals. By immunofluorescence microscopy, surface-associated P-selectin was present in patches on eosinophils, some of which stained for the platelet marker thrombospondin-1. Activated ?(1) and P-selectin partially colocalized on eosinophils. Soluble P-selectin added to whole blood enhanced activation of eosinophil ?(1), but not ?(2), integrins. In contrast, IL-5 activated eosinophil ?(2), but not ?(1), integrins. Eosinophils that did not attach to vascular cell adhesion molecule-1 (VCAM-1) in a static adhesion assay had a lower N29 signal than the original population. Soluble P-selectin added to whole blood enhanced eosinophil adhesion to VCAM-1. These findings are compatible with a scenario whereby P-selectin, on eosinophil-associated activated platelets or acquired from plasma or from prior interactions with endothelial cells or platelets, activates eosinophil ?(4)?(1) integrin and stimulates eosinophils to adhere to VCAM-1 and move to the airway in asthma.

SUBMITTER: Johansson MW 

PROVIDER: S-EPMC3208615 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature