Abstract
Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease that is currently the third leading cause of death worldwide. Recent reports have indicated that dysfunctional iron handling in the lungs of COPD patients may be one contributing factor. However, a number of these studies have been limited to the qualitative assessment of iron levels through histochemical staining or to the expression levels of iron-carrier proteins in cells or bronchoalveolar lavage fluid. In this study, we have used time of flight secondary ion mass spectrometry (ToF-SIMS) to visualize and relatively quantify iron accumulation in lung tissue sections of healthy donors versus severe COPD patients. An IONTOF 5 instrument was used to perform the analysis, and further multivariate analysis was used to analyze the data. An orthogonal partial least squares discriminant analysis (OPLS-DA) score plot revealed good separation between the two groups. This separation was primarily attributed to differences in iron content, as well as differences in other chemical signals possibly associated with lipid species. Further, relative quantitative analysis revealed twelve times higher iron levels in lung tissue sections of COPD patients when compared to healthy donors. In addition, iron accumulation observed within the cells was heterogeneously distributed, indicating cellular compartmentalization.
Highlights
Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease encompassing airway inflammation, destruction of lung tissue and remodeling of the small airways[1]
We employed ToF-SIMS imaging to map the distribution of iron within the complex anatomy of human lung tissue obtained from healthy donors and very severe COPD patients (GOLD IV)
Hematoxylin and Eosin (H&E) staining was performed on healthy donors (Fig. 1a) and COPD patients (Fig. 1d) lung tissue sections to reveal the cellular distribution (pink and purple staining) pattern of the tissue sections
Summary
Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease encompassing airway inflammation (chronic bronchitis), destruction of lung tissue (emphysema) and remodeling of the small airways[1]. We have employed time of flight secondary ion mass spectrometry (ToF-SIMS) to visualize and relatively quantify iron accumulation in human lung tissue sections of COPD (GOLD IV) patients versus (vs.) healthy donors. Over the recent years this technique has been introduced for biomedical studies on human tissue samples such as liver[22], kidney[23], skeletal muscle[24] and various forms of cancer such as prostate cancer[25] and breast cancer[26] In this technique, a microfocused beam is impinged on discrete points of a sample surface, generating secondary ions that are analyzed to generate a mass spectrum at each pixel point from the sample. The extracted secondary ions from the sample surface are collected with a certain delay after the arrival of primary ions[30], which makes it possible to record secondary ion images of ion species with very high spatial resolution and a mass resolution of several thousands in a single run
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