Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix

Abstract

Background Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects.MethodsIn an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC–MS/MS and a targeted selected reaction monitoring LC–MS/MS analyzing 130 proteins and four in vivo peptide degradation products.ResultsThe analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways.ConclusionExposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.Electronic supplementary materialThe online version of this article (10.1186/s12014-018-9196-y) contains supplementary material, which is available to authorized users.

Biomonitoring of Metal Exposure During Additive Manufacturing (3D Printing)

“…The levels of both nanoparticles (average size in general between 50 and 100 nm, as measured using the Nanotracer) and slightly larger particles (0.3 μm measured using the Lighthouse) were constantly much higher in the welding facility compared with the AM facility. High levels of nanoparticles in welding facilities are in line with what we found in the pilot study [7] and what is known from recent studies focusing on welding [15]. This may depend on the fact that in the welding facility, there are a wide array of different processes including welding, metal cutting, and combustion engines that may contribute to the bulk of produced small particles.…”

“…However, the levels of 10-μm particles in the AM facility must not be neglected because these particles could still be harmful if inhaled or ingested. Inhalation of metal particles alters nasal lavage fluid acute-phase proteins [15] and may increase cancer risk in the lungs, kidneys, and bladder [18].…”

Metal exposure from additive manufacturing and its effect on the nasal lavage fluid proteome - a pilot study

“…WAP four-disulfide core domain protein 2 (Wfdc2) is an endopeptidase inhibitor known to be expressed in the respiratory tract. An earlier study of NLF from welders showed a decrease of Wfdc2 after controlled chamber exposure to welding fumes [ 19 ], similar to what we found in AM operators during year 1. Like Jchain, Wfdc2 was shown to be decreased in the nasal mucosa of individuals with allergic rhinitis as compared to healthy controls [ 25 ].…”

“…NLF constitutes an interesting matrix to identify early markers of exposure in the upper airways that could precede health effects. As such, it has previously been used in chamber studies of welding fumes [ 19 ] but is entirely novel for the much less studied AM environment. In this pilot study, the protein levels in NLF were investigated in AM operators and welders at two time points during a single workweek over two consecutive years.…”

“…Due to its non-invasive nature, it is interesting for the use of finding markers for diseases and exposure including early markers of exposure that could precede eventual health effects. As such it has been applied to find changes in protein content (proteomic alterations) due to smoking [ 14 ] and allergic rhinitis [ 15 ] as well as in a range of occupational exposures including epoxy chemicals [ 16 ], trichloramine in swimming pool facilities [ 17 ], metalworking fluids [ 18 ], welding fumes [ 19 ], hairdressing chemicals [ 20 ] and chemical and biological agents released in moldy and damp buildings [ 21 ].…”