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Am J Respir Crit Care Med. 2012 Mar 1;185(5):498-507. doi: 10.1164/rccm.201109-1712OC. Epub 2012 Jan 6.

Platelet activation, P-selectin, and eosinophil β1-integrin activation in asthma.

Author information

1
Department of Biomolecular Chemistry, University of Wisconsin, Madison, 53706, USA. mwjohansson@wisc.edu

Abstract

RATIONALE:

Eosinophil β1-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma.

OBJECTIVES:

Determine the relationships between β1-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 β1-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 β1-integrin correlated with eosinophil-bound P-selectin among all subjects with asthma even though activated β1-integrin was higher in subjects with nonsevere asthma than severe asthma. Activated β1-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 β1-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 β1-integrin disappeared.

CONCLUSIONS:

The relationship between eosinophil β1-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 β1-integrin activation occur in both nonsevere and severe asthma with rapid movement of platelet-eosinophil complexes into the lung in more severe disease.

PMID:
22227382
PMCID:
PMC3297102
DOI:
10.1164/rccm.201109-1712OC
[Indexed for MEDLINE]
Free PMC Article

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