The determination of possible biomarkers in nasal secretion of healthy subjects can have a role in early diagnosis of diseases such as rhinosinusitis. For this purpose, nasal lavage fluids (NLFs) from ten volunteers, collected before and after they had been submitted to nasal provocations, were investigated. Separation and analysis of proteins present in this complex matrix was performed using a capillary liquid chromatography-electrospray-quadrupole-time of flight mass spectrometry equipment. From among a total of 111 proteins found (89 known and two unknown proteins), 42 of which had never been previously described in this fluid, such as Deleted in Malignant Brain Tumors 1 isoform a precursors, and cytoskeletal proteins were identified with high statistical score. Three proteins of palate lung nasal epithelial clone (PLUNC) family: SPLUNC1, LPLUNC1, and LPLUNC2 were identified. Proteins involved in innate (27%) and acquired immunity (21%) systems were major components of NLF. Cellular (52% of all proteins identified) such as cytoskeletal (33%), functional (15%), and regulatory (4%) proteins, normally present in the nasal cavity, have also been identified. The proteomic approach presented here allowed us to identify the proteins involved in acquired and innate immune response in the nose against microbial infections and unclean inhaled air.
Desmosine (DES) and isodesmosine (IDES) are two unusual, tetrafunctional, pyridinium ring-containing amino acids involved in elastin cross-linking. Being amino acids unique to mature, cross-linked elastin, they are useful for discriminating peptides derived from elastin breakdown from precursor elastin peptides. According to these features, DES and IDES have been extensively discussed as potentially attractive indicators of elevated lung elastic fibre turnover and markers of the effectiveness of agents with the potential to reduce elastin breakdown. In the present manuscript, immunology-based and separation methods for the evaluation of DES and IDES are discussed, along with studies reporting increased levels of urine excretion in chronic obstructive pulmonary disease (COPD) patients with and without a 1 -antitrypsin deficiency. The results of the application of DES and IDES as surrogate end-points in early clinical trials in COPD are also reported. Finally, recent advances in detection techniques, including liquid chromatography tandem mass spectrometry and high-performance capillary electrophoresis with laser-induced fluorescence, are discussed. These techniques allow detection of DES and IDES at very low concentration in body fluids other than urine, such as plasma or sputum, and will help the understanding of whether DES and IDES are potentially useful in monitoring therapeutic intervention in COPD.
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