Evaluación de la producción de trampas extracelulares de neutrófilos (NETs) en población adulta expuesta a plomo

Abstract

Lead is a heavy metal that has been widely used due to its physical and chemical properties. Although its use has been restricted, sources of exposure have been identified to date in Mexico, with lead-glazed earthenware being a common source. One of the body systems primarily affected is the immune system, and the main mechanism involved is the production of oxidative stress. Currently there are few reports regarding the effects of lead on neutrophils, especially on NETs, which are web-shaped structures composed of DNA and proteins. It is suggested that lead can favour the production of NETs by the generation of reactive oxygen species (ROS), which are necessary for its formation. Therefore, the aim of this study was to evaluate the plasma levels of NETs markers in a population occupationally exposed to lead. To achieve this, 50 potters from the community of San Pablo del Monte in the State of Tlaxcala, Mexico, were studied. A sample of 10.0 mL of whole blood was collected and plasma was isolated. The blood lead levels (BLL) were measured by graphite furnace atomic absorption spectrophotometry (GFAAS) and plasma was used to evaluate malondialdehyde (MDA) levels by the 1M2F assay, myeloperoxidase (MPO) and histone H3 citrullinated (CitH3) levels by ELISA and cell-free DNA (cfDNA) levels by a fluorescence assay. In addition, plasma inflammatory cytokines levels were quantified using a CBAs kit via flow cytometry. As results, we found a mean BLL of 12.04 ± 6.11 μg/dL. Potter population was divided into two groups: a high-exposure group (BLL ≥ 10 μg/dL, n=30) and a low-exposure group (BLL <10 μg/dL, n=20). Higher plasma levels of cfDNA were found in the high-exposure group compared to the low-exposure group (408.9 ± 90.99 vs 345.8 ± 89.46 ng/mL, p<0.001). Notably, a significant positive correlation between BLL and cfDNA (r = 0.31, p=0.04) was found in the potter’s population. Regarding NET markers, a positive correlation was found between cfDNA/citH3 (r =0.38, p=0.037), and cfDNA/MPO (r =0.37, p=0.04) in the high-exposure group. Noteworthy, IL-8 was detected in seven potters from the high-exposure group (25.91 ± 14.08 pg/mL). In conclusion, potters with blood lead levels ≥10 μg/dL produce and release NETs into the bloodstream. The potential clinical implications of these findings are an issue that deserves further investigation.