Induced sputum proteome in healthy subjects and asthmatic patients

Abstract

Background Asthma is a heterogeneous disease characterized by abnormal airway pathophysiology and susceptibility to different stimuli, as exemplified by a subset of individuals with exercise-induced bronchoconstriction (EIB). Induced sputum provides a noninvasive method to sample airway biofluids that are enriched in proteins. Objective We hypothesized that novel mechanisms in the pathogenesis of asthma may be revealed by studying the patterns of protein expression in induced sputum. Methods We used shotgun proteomics to analyze induced sputum from 5 normal individuals and 10 asthmatics, including 5 with EIB. Differential protein expression between asthmatics, asthma subphenotypes and control subjects was determined using spectral counting and computational methods. Results Using Gene Ontology analysis, we defined the functional landscape of induced sputum proteome and applied network analysis to construct a protein interaction map for this airway compartment. Shotgun proteomics analysis identified a number of proteins whose differential enrichment or depletion robustly distinguishedasthmatics from normal controls, and captured the effects of exercise on induced sputum proteome. Functional and network analysis identified key processes, including proteolytic activity that are known contributors to airway remodeling. Importantly, this approach highlighted previously unrecognized roles for differentially expressed proteins in pathways implicated in asthma, such as modulation of phospholipase A2 by secretoglobin, a putative role for S100A8/9 in human asthma, and selective upregulation of complement 3a in response to exercise in asthmatics. Conclusion Computationally-intensive analysis of induced sputum proteome is a powerful approach to understand the pathophysiology of asthma and a promising methodology to investigate other diseases of the airways.

Resolving the etiology of atopic disorders by using genetic analysis of racial ancestry

“…255 More recent approaches include shotgun proteomics, which has been used to characterize protein patterns in induced sputum from asthmatic patients, including patients with exercise-induced asthma. 256 While we are not aware of any studies exploring the use of proteomics to characterize the relationship between race and allergic disease, peptide profiles and protein signatures that are specifically associated with several different cancer forms in patients of African ancestry have been identified. 257,258 Similarly, we can expect proteomics to play a future role in explaining racial disparities and identifying race-specific biomarkers associated with allergic disease.…”

Decreased S100A9 Expression Promoted Rat Airway Smooth Muscle Cell Proliferation by Stimulating ROS Generation and Inhibiting p38 MAPK

“…S100A9 has also been identified as a key mediator in mucin hyperproduction of neutrophil-dominant airway inflammation [20]. In asthmatic patients, S100A9 expression was downregulated in sputum [21]. However, S100A9 level was elevated in serum of bakery workers and involved in innate immune responses of baker's asthma pathogenesis [22].…”

Comparative proteomics of inhaled silver nanoparticles in healthy and allergen provoked mice

“…26 We investigated the protein profiles in BALF and plasma after AgNP inhalation by healthy (control) and diseased (OVA-sensitized allergy) mouse models. The gas-phase fractionation method was used to increase proteome coverage and the reproducibility of peptide ion selection by direct MS analysis of the peptides produced by proteolytic digestion of unfractionated proteins from the BALF and plasma samples.…”