Dataset Information

Platelet activation, P-selectin, and eosinophil ?1-integrin activation in asthma.

ABSTRACT: Eosinophil ?1-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma.Determine the relationships between ?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.Blood was assayed by flow cytometry for P-selectin and activated ?1-integrin on eosinophils and platelets. Plasma was analyzed with ELISA for soluble P-selectin, platelet factor 4, and thrombospondin-1.Activated ?1-integrin correlated with eosinophil-bound P-selectin among all subjects with asthma even though activated ?1-integrin was higher in subjects with nonsevere asthma than severe asthma. Activated ?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 ?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 ?1-integrin disappeared.The relationship between eosinophil ?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 ?1-integrin activation occur in both nonsevere and severe asthma with rapid movement of platelet-eosinophil complexes into the lung in more severe disease.

SUBMITTER: Johansson MW

PROVIDER: S-EPMC3297102 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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

Johansson Mats W MW Han Shih-Tsung ST Gunderson Kristin A KA Busse William W WW Jarjour Nizar N NN Mosher Deane F DF

American journal of respiratory and critical care medicine 20120106 5

<h4>Rationale</h4>Eosinophil β1-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma.<h4>Objectives</h4>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.<h4>Methods</h4>Blood was assayed by flow cytometry for P-selectin and activated β1-integrin on eo ...[more]

PMID: 22227382

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Project description:Eosinophilic inflammation is one of the main pathophysiological features in asthma. Two subtypes of eosinophils exist in the lung and systemic circulation: lung-resident eosinophils (rEOS) and inflammatory eosinophils (iEOS). We evaluated the expression of α4β1 and αMβ2 integrins of eosinophil subtypes and their influence on airway smooth muscle (ASM) cell proliferation and viability in asthma. We included 16 severe non-allergic eosinophilic asthma (SNEA) patients, 13 steroid-free, non-severe allergic asthma (AA) patients, and 12 healthy control subjects (HS). For AA patients, a bronchial allergen challenge with Dermatophagoides pteronyssinus was performed. The eosinophil subtypes were distinguished using magnetic bead-labeled antibodies against surface CD62L, and individual combined cell cultures were prepared with ASM cells. The integrins gene expression was analyzed by a quantitative real-time polymerase chain reaction. Proliferation was assessed by the Alamar blue assay, and viability by annexin V and propidium iodide staining. rEOS-like cells were characterized by the relatively higher gene expression of the β1 integrin subunit, whereas iEOS-like cells were characterized by the αM and β2 integrin subunits. The inclusion of either eosinophil subtypes in co-culture significantly increased the proliferation of ASM cells, and the effect of rEOS-like cells was stronger than iEOS-like cells (p < 0.05). Furthermore, rEOS-like cells had a more pronounced effect on reducing ASM cell apoptosis compared to that of iEOS-like cells (p < 0.05). Lastly, the bronchial allergen challenge significantly enhanced only the iEOS-like cells' effect on ASM cell proliferation and viability in AA patients (p < 0.05). These findings highlight the different expression of α4β1 and αMβ2 integrins on distinct eosinophil subtypes in asthma. Therefore, rEOS-like cells have a stronger effect in stimulating ASM cell proliferation and viability; however, contact with specific allergens mainly enhances pro-proliferative iEOS-like cell properties.

Dataset Information

Platelet activation, P-selectin, and eosinophil ?1-integrin activation in asthma.

Publications

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

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