Low concentrations of lead disturb phenotypical markers of the inflammatory and the anti-inflammatory profile of bone marrow-derived macrophages from BALB/c mice

Abstract

Lead (Pb) is a ubiquitous toxic metal that decreases resistance to infections, in which the macrophages have an essential role. Pb adverse effects on nitric oxide (NO^-) production and variable effects on inflammatory cytokines in activated macrophages have been reported, but no effects have been reported in anti-inflammatory macrophages. We studied Pb (0.03-6 μg/dL equivalent to 0.014-2.89 μM) effects on the function of bone marrow-derived macrophages (BMDM) induced to either inflammatory or anti-inflammatory phenotypes, with LPS + IFNγ or IL-4+IL-13, respectively, and whether these effects are related. Pb did not induce cytotoxicity at any concentration in both macrophage phenotypes. In inflammatory BMDM, Pb (6 μg/dL) inhibited NO^- production without affecting inducible nitric oxide synthase (iNOS) levels or basal arginase activity. At 3 and 6 μg/dL, Pb enhanced the major histocompatibility complex class II (MHC II) membrane expression but did not modify CD86 expression, TNFα, or IL-1β production and secretion. In anti-inflammatory BMDM, Pb did not alter arginase activity, but at 3 and 6 μg/dL, increased TGF-β1 and mannose receptor expression. Results showed that environmentally relevant concentrations of Pb alter functional outcomes or phenotypic markers of anti-inflammatory for the first time. The Pb effects on the inflammatory macrophages are not dependent on negative feedback resulting from the Pb effect on the anti-inflammatory phenotype. The Pb affected only some molecules or specific pathways related to both phenotypes. These effects could be related to Pb effects on immune defense against intracellular pathogens and allergy susceptibility.

Keywords: Anti-inflammatory macrophages; Inflammatory macrophages; Lead (Pb); Macrophages.