Asthma Sample Collection Protocol: Defining the Role of Apolipoprotein Pathways in Asthma

National Heart, Lung, And Blood Institute

Investigators

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Abstract

The progress achieved under this protocol is summarized as follows: 1. The structural cell populations obtained by this protocol have been utilized to characterize the expression of ARTS-1 in lung cell populations. Bronchial epithelial cells that have been obtained by bronchial brushings have been utilized to demonstrate co- localization of membrane-associated ARTS-1 and TNFR1 in the apical cell membrane of ciliated bronchial epithelial cells. 2. Bronchoalveolar lavage fluid obtained by this protocol has been utilized to identify exosome-like vesicle release as a new mechanism by which soluble cytokine receptors can be generated, independent of ectodomain cleavage by receptor sheddases. The majority of soluble type I TNF receptor (TNFR1) in bronchoalveolar lavage fluid was found to be full-length, 55-kDa, exosome-associated TNFR1, whereas the 28-kDa cleaved TNFR1 ectodomain represented only a minor fraction. Thus, release of exosome-associated TNFR1 (i.e., eTNFR1) represents an important alternative mechanism for the release of soluble TNF receptors. 3. BAL fluid from asthmatic patients has been utilized in studies investigating the ADP-ribosyltransferase-specific modification of human neutrophil peptide-1. 4. Expression of the VLDL receptor was demonstrated for the first time on circulating CD11c+/CD14-/HLA-DR+ dendritic cells. This confirmed our result in a murine model that the VLDL receptor is expressed by dendritic cells and attenuates house dust mite-induced airway inflammation by suppressing dendritic cell-mediated adaptive immune responses. 5. BAL fluid cells have been used to show that expression of CD163 is reduced on alveolar macrophages from asthmatics as compared to normal subjects. 6. Induced sputum cells have been used to develop components of a nanoscale microfluidic flow cytometer that will liquefy sputum samples for point-of-care inflammatory phenotyping of asthmatic patients. 7. Myeloid dendritic cell subsets from patients with eosinophil-high asthma were shown to have lower levels of LRP-1 expression than those from healthy nonasthmatic subjects and that a negative correlation exists between LRP-1 expression by myeloid dendritic cell subsets and peripheral blood eosinophil counts in asthmatic patients. 8. HDL particles were shown to be negatively correlated, whereas serum triglycerides were shown to be positively correlated, with blood eosinophils in atopic asthmatics. This supports the concept that serum levels of HDL and triglycerides may be linked to systemic type 2 inflammation in atopic asthma.