ToF-SIMS mediated analysis of human lung tissue reveals increased iron deposition in COPD (GOLD IV) patients

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.

Study of the diacylglycerol composition in the liver and serum of mice with prediabetes and diabetes using MeV TOF-SIMS

“…Our results are in agreement with the TOF-SIMS results obtained on the tissue samples of people suffering from non-alcoholic fatty liver disease [15,32,33]. Additionally, the method is successfully applied to image the location and to quantify a single compound or even a set of compounds in diseases such as colon dysplasia, osteoporosis, breast cancer or chronic obstructive pulmonary disease [34][35][36][37]. To our knowledge, the only work in which TOF-SIMS was used to identify the changes in the lipid composition within mouse tissue (skeletal muscle, liver and adipose tissue) in response to the dietary intake of omega-3 fatty acids was published by Sjovall et al [2].…”

The Significance of iron deficiency and anemia in a real-life COPD cohort

“…In this context, it is essential to distinguish between local and systemic iron dyshomeostasis. Previous studies showed high iron content in lung tissues of advanced COPD patients compared to healthy controls, with a heterogeneous distribution of iron at a cellular level, including mitochondria [34]. Mitochondrial iron loading has previously been linked to COPD, as it is upregulated by iron-responsive element-binding protein 2, which is increased in COPD.…”

Controlling orientation, conformation, and biorecognition of proteins on silane monolayers, conjugate polymers, and thermo-responsive polymer brushes: investigations using TOF-SIMS and principal component analysis

“…PCA could also be applied to an analysis of TOF-SIMS 2D images [33,[58][59][60] and even 3D TOF-SIMS sputtering data [50]. Other multivariate methods already applied for TOF-SIMS data analysis are non-negative matrix factorization (NMF) [61,62], the k-means cluster method [63], discriminant analysis [64,65], and artificial neuronal networks [55,66] involving self-organizing maps [67][68][69][70][71].…”