title: Activation of beta1 integrins on blood eosinophils by P-selectin.
abstract: Activation of β(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 β(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-β(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 β(1) and P-selectin partially colocalized on eosinophils. Soluble P-selectin added to whole blood enhanced activation of eosinophil β(1), but not β(2), integrins. In contrast, IL-5 activated eosinophil β(2), but not β(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 α(4)β(1) integrin and stimulates eosinophils to adhere to VCAM-1 and move to the airway in asthma.
authors: Department of Biomolecular Chemistry, University of Wisconsin, 4285A, Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA. mwjohansson@wisc.edu
authors: Mats W
authors: MW
authors: Johansson
authors: Deane F
authors: DF
authors: Mosher
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D002448:Cell Adhesion; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005541:Forced Expiratory Volume; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000503:physiopathology; D008297:Male; D008856:Microscopy, Fluorescence; D019007:P-Selectin / Q000378:metabolism*; D012720:Severity of Illness Index; D019700:Thrombospondin 1 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014922:Wisconsin; D055815:Young Adult
chemical_list: D019012:Integrin beta1; D015848:Interleukin-5; D019007:P-Selectin; C546937:SELP protein, human; D019700:Thrombospondin 1; D019010:Vascular Cell Adhesion Molecule-1