Dataset Information

Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages.

ABSTRACT: The aim of this study was to assess the influence of lead (Pb) at low concentrations (imitating Pb levels in human blood in chronic environmental exposure to this metal) on interleukin 1? (IL-1?) and interleukin 6 (IL-6) concentrations and the activity and expression of COX-1 and COX-2 in THP-1 macrophages. Macrophages were cultured in vitro in the presence of Pb at concentrations of: 1.25 ?g/dL; 2.5 ?g/dL; 5 ?g/dL; 10 ?g/dL. The first two concentrations of Pb were selected on the basis of our earlier study, which showed that Pb concentration in whole blood (PbB) of young women living in the northern regions of Poland and in the cord blood of their newborn children was within this range (a dose imitating environmental exposure). Concentrations of 5 ?g/dL and 10 ?g/dL correspond to the previously permissible PbB concentrations in children or pregnant women, and adults. Our results indicate that even low concentrations of Pb cause an increase in production of inflammatory interleukins (IL-1? and IL-6), increases expression of COX-1 and COX-2, and increases thromboxane B2 and prostaglandin E2 concentration in macrophages. This clearly suggests that the development of inflammation is associated not only with COX-2 but also with COX-1, which, until recently, had only been attributed constitutive expression. It can be concluded that environmental Pb concentrations are able to activate the monocytes/macrophages similarly to the manner observed during inflammation.

SUBMITTER: Metryka E

PROVIDER: S-EPMC7139839 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages.

Metryka Emilia E Kupnicka Patrycja P Kapczuk Patrycja P Simińska Donata D Tarnowski Maciej M Goschorska Marta M Gutowska Izabela I Chlubek Dariusz D Baranowska-Bosiacka Irena I

International journal of molecular sciences 20200324 6

The aim of this study was to assess the influence of lead (Pb) at low concentrations (imitating Pb levels in human blood in chronic environmental exposure to this metal) on interleukin 1β (IL-1β) and interleukin 6 (IL-6) concentrations and the activity and expression of COX-1 and COX-2 in THP-1 macrophages. Macrophages were cultured in vitro in the presence of Pb at concentrations of: 1.25 μg/dL; 2.5 μg/dL; 5 μg/dL; 10 μg/dL. The first two concentrations of Pb were selected on the basis of our e ...[more]

PMID: 32214022

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Project description:Determination of Pb-210 (210Pb) in aqueous solution is a common radioanalytical challenge in environmental science. Widely used methods for undertaking these analyses (e.g., ASTM D7535) rely on the use of stable lead (Pb) as a yield tracer that takes into account losses of 210Pb that inevitably occur during elemental/radiochemical separations of the procedures. Although effective, these methods introduce technical challenges that can be difficult to track and potentially introduce uncertainty that can be difficult to quantify. Examples of these challenges include interference from endogenous stable Pb in complex sample matrices; contamination of stable Pb carrier with 210Pb; and high detection limits due to counting efficiency limitations. We hypothesized that many of these challenges could be avoided by the use of the electron-capture, gamma-emitting isotope, 203Pb as a chemical yield tracer in the analysis of 210Pb. A series of experiments were performed to evaluate the efficacy of 203Pb as a tracer. Four different matrices were analyzed, including a complex matrix (hydraulic-fracturing produced fluids); and samples comprising less complicated matrices (i.e., river water, deionized water, and tap water). Separation techniques and counting methodologies were also compared and optimized. Due to a relatively short-half life (52 h), 203Pb tracer is effectively massless for the purposes of chemical separations, allowing for reduced chromatography column resin bed volumes. Because 203Pb is a gamma emitter (279 keV; 81% intensity), recovery can be determined non-destructively in a variety of matrices, including liquid scintillation cocktail. The use of liquid scintillation as a counting methodology allowed for determination of 210Pb activities via 210Pb or 210Po; and recoveries of greater than 90% are routinely achievable using this approach. The improved method for the analysis of 210Pb in aqueous matrices allows for the analysis of complex matrices, at reduced cost, while providing greater counting flexibility in achieving acceptable detections limits.

Project description:BACKGROUND: The pathological hallmark of multiple sclerosis (MS) is myelin phagocytosis. It remains unclear why microglia and macrophages demyelinate axons in MS, but previously found or yet-unknown changes in the myelin of MS patients could contribute to this process. We therefore studied whether myelin from normal-appearing white matter (NAWM) of MS donors is phagocytosed more efficiently than myelin from control donors. METHODS: Myelin was isolated from 11 MS and 12 control brain donors and labeled with the pH-sensitive fluorescent dye pHrodo to quantify uptake in lysosomes. Phagocytosis by differentiated THP-1 macrophages and by primary human microglia was quantified with flow cytometry. Whereas myelin uptake by THP-1 macrophages reached a plateau after approximately 24 hours, uptake by primary human microglia showed an almost linear increase over a 72-hour period. Data were statistically analyzed with the Mann-Whitney U test. RESULTS: MS-derived myelin was phagocytosed more efficiently by THP-1 macrophages after 6-hour incubation (P?=?0.001 for the percentage of myelin-phagocytosing cells and P?=?0.0005 for total myelin uptake) and after 24-hour incubation (P?=?0.0006 and P?=?0.0001, respectively), and by microglia after 24-hour incubation (P?=?0.0106 for total myelin uptake). This enhanced uptake was not due to differences in the oxidation status of the myelin. Interestingly, myelin phagocytosis correlated negatively with the age of myelin donors, whereas the age of microglia donors showed a positive trend with myelin phagocytosis. CONCLUSIONS: Myelin isolated from normal-appearing white matter of MS donors was phagocytosed more efficiently than was myelin isolated from control brain donors by both THP-1 macrophages and primary human microglia. These data indicate that changes in MS myelin might precede phagocyte activation and subsequent demyelination in MS. Identifying these myelin changes responsible for enhancing phagocytic ability could be an interesting therapeutic target to prevent or inhibit formation or expansion of MS lesions. Moreover, during aging, microglia enhance their phagocytic capacity for myelin phagocytosis, but myelin reduces its susceptibility for uptake.

Dataset Information

Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages.

Publications

Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages.

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