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


OBJECTIVE
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.


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.
Department of Biomolecular Chemistry, University of Wisconsin, Madison, 53706, USA. mwjohansson@wisc.edu
Mats W
MW
Johansson
Shih-Tsung
ST
Han
Kristin A
KA
Gunderson
William W
WW
Busse
Nizar N
NN
Jarjour
Deane F
DF
Mosher
D000328:Adult; D001249:Asthma / Q000097:blood / Q000503:physiopathology*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000097:blood / Q000502:physiology*; D008297:Male; D019007:P-Selectin / Q000097:blood / Q000502:physiology*; D015539:Platelet Activation / Q000502:physiology*; D010978:Platelet Factor 4 / Q000097:blood; D019700:Thrombospondin 1 / Q000097:blood
D019012:Integrin beta1; D019007:P-Selectin; D019700:Thrombospondin 1; D010978:Platelet Factor 4