Relationship between pulmonary and systemic markers of exposure to multiple types of welding particulate matter
Introduction
Epidemiological studies have shown increased cardiovascular mortality and morbidity following particulate matter exposure (Brook et al., 2010, Dockery et al., 1993, Pope et al., 1992, Samet et al., 2000, Schwartz and Morris, 1995). Subsequent human and animal studies support these findings: therefore, biological mechanisms have been proposed to explain the effects. First, the direct mechanism hypothesizes that particles, most likely ultrafine in size, and/or soluble metals or organic compounds enter the circulation and induce biological effects (Brook et al., 2010, Nemmar et al., 2001, Nemmar et al., 2002, Oberdorster et al., 2002). Second, an indirect mechanism is activation of the autonomic nervous system resulting in an imbalance between sympathetic and parasympathetic stimulation (Brook et al., 2010, Gold et al., 2000, Magari et al., 2001, Pope et al., 1999). Finally, another proposed indirect effect is that particle exposure results in a pulmonary inflammatory response and release of mediators into the general circulation (Brook et al., 2010, Seaton et al., 1995). These mechanisms may combine to produce effects including endothelial dysfunction, decreased heart rate variability, enhanced coagulation potential and increased progression of atherosclerosis (Brook et al., 2010). While the indirect hypothesis of spill-over of pulmonary inflammation has the strongest mechanistic support, to some degree, all three mechanisms may work in concert to produce systemic effects (Brook et al., 2010).
Welding results in a unique and complex occupational exposure. The aerosol generated from welding contains both gases and a fume which consists of metal oxide particulate matter (Antonini, 2003). The contents of these fractions will vary depending on the type of welding performed. Therefore, the potential exists for varying pulmonary effects for different welding processes. In addition, extrapulmonary effects of welding have been described including an increased risk for cardiovascular disease (Hilt et al., 1999, Ibfelt et al., 2010, Moulin et al., 1993, Newhouse et al., 1985, Sjogren et al., 2002, Suadicani et al., 2002). Supportingly, adverse cardiovascular effects in response to metal-rich particulate matter exposure, such as residual oil fly ash (Campen et al., 2000, Campen et al., 2002, Farraj et al., 2011, Kodavanti et al., 2002, Nurkiewicz et al., 2004, Watkinson et al., 1998), strengthen the likelihood of welding fume-induced systemic effects. In this study we compared three different welding fumes including manual metal arc stainless steel (MMA-SS), gas metal arc-SS (GMA-SS) or GMA-mild steel (GMA-MS). The MMA-SS welding fume contains soluble metals, primarily chromium, while the GMA-SS contains primarily insoluble metals that persist in the lung. The GMA-MS, a common welding fume used in industry and considered the least toxic of the three described here, also has limited solubility.
Recently we showed that pulmonary exposure to the engineered nanoparticle, carbon nanotubes (CNT), resulted in adverse cardiovascular effects (Erdely et al., 2009, Li et al., 2007, Simeonova and Erdely, 2009). Pulmonary exposure to CNT caused distressed aortic mitochondrial homeostasis and increased plaque lesion area in apolipoprotein E knockout mice which indicated systemic oxidative stress and inflammation (Li et al., 2007). Subsequent studies revealed a systemic inflammatory response, measured as blood gene expression, elevated serum cytokines and chemokines and vascular inflammation (Erdely et al., 2009). These data demonstrated a lung and systemic crosstalk in response to the exposure illustrating that indirect, pulmonary-derived inflammation contributed significantly to cardiovascular effects. Here, similar methodology as our CNT study was applied to investigate the differences between the systemic inflammatory responses of three welding fumes. Also, in anticipation of systemic effects, various parameters of pulmonary inflammation and toxicity were examined to yield mechanistic insight into these effects.
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Animals and exposure conditions
Male C57BL/6 mice (Jackson Laboratory, Bar Harbor, ME) 10–12 weeks of age were used in this study. All mice were provided food (Teklad 7913) and tap water ad libitum in ventilated cages in a controlled humidity and temperature environment with a 12 h light/dark cycle. Animal care and use procedures were conducted in accordance with the “PHS Policy on Humane Care and Use of Laboratory Animals” and the “Guide for the Care and Use of Laboratory Animals” (NIH publication 86-23, 1996). These
Metal translocation
Following pulmonary exposure to welding fume there was rapid translocation of metals from the lung. The primary soluble component of the MMA-SS fume, chromium, was evident in the kidney (2.20 ± 0.38 μg/g PBS vs 13.87 ± 1.17* MMA-SS; *p < 0.05) and liver (2.51 ± 0.11 μg/g PBS vs 4.40 ± 0.46* MMA-SS; *p < 0.05) at 4 h post-exposure. Increased levels of manganese were found in the kidney after GMA-SS exposure (5.43 ± 0.24 μg/g PBS vs 7.56 ± 0.56* GMA-SS; *p < 0.05). There were no changes in other metals, including
Discussion
The findings of this study show that various types of welding fume result in different toxicities in the lung which thereby may influence systemic inflammation. While all fumes had increased pulmonary inflammatory gene expression within hours after exposure, the response was greater at 24 h in the SS fumes but not in the GMA-MS fume. In a corresponding fashion the SS fumes showed evidence of systemic inflammation. Interestingly, only the MMA-SS fume was able to induce stress response genes in
Conflict of interest
There are none.
Acknowledgements
Special thanks to Dr. Vincent Castranova, Dr. Jane Ma and Dr. Paul Nicolaysen for their review of the manuscript.
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