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Published on: August 12, 2019
Lead modulation of macrophages causes multiorgan detrimental health effects
Jane Kasten-Jolly1, David A Lawrence
1Wadsworth Center, New York State Department of Health, Albany, NY, 12208, USA.
Abstract:
The environmental toxicant lead (Pb) has detrimental effects on a number of organ systems, including the immune system. Pb exposure decreases host immune defenses against numerous microorganisms and cancer. Although Pb effects on humoral and cell-mediated immunity as well as on erythrocyte, neural, and renal pathophysiology have been well documented, there are few reports regarding Pb's impact on innate immunity, which can affect multiorgan processes. This review focuses on Pb modulation of a key innate immune cell, the macrophage. The impact of Pb on macrophages in different organs, on immature versus mature macrophages, and on low versus high Pb concentrations is discussed. Pb decreases phagocytosis and chemotaxis of macrophages and affects nitric oxide production and eicosanoid metabolism in mature macrophages. Pretreatment of macrophages with Pb increases TNF-α secretion after in vitro stimulation with lipopolysaccharide; however, Pb exposure decreases in vivo intracellular pathogen killing. More recent evidence from mouse studies indicates that even low, environmentally relevant, blood concentrations of Pb result in increased phagocytosis of erythrocytes and decreased expression of interferon-gamma-inducible GTPases, p65-GBP, and p47-IRG, which are necessary for intracellular pathogen killing. Taking into account the effects of Pb on macrophages, the review describes posited mechanisms to account for Pb-altered health effects; Pb effects on heme levels may play a key role as well as Pb's preferential induction of helper type-2 T (Th2) cells and M2 macrophages, which is related to oxidative stress. The discussion links old findings with new, thereby adding new insight into the effects of Pb on macrophages and the resultant compromised immunity and health.
Insights
Lead (Pb) exposure impairs innate immunity by affecting macrophages, crucial immune cells. This review details how lead impacts macrophage function, potentially compromising the body's defense against pathogens and contributing to health issues.
Area of Science:
- Immunology
- Environmental Toxicology
- Innate Immunity
Background:
- Lead (Pb) is an environmental toxicant with known detrimental effects on multiple organ systems, including the immune system.
- While Pb's impact on adaptive immunity and other organ systems is documented, its effects on innate immunity, particularly macrophages, are less understood.
- Innate immunity plays a critical role in host defense against pathogens and in regulating multiorgan processes.
Purpose of the Study:
- To review the modulation of macrophages, a key innate immune cell, by lead (Pb) exposure.
- To discuss the impact of Pb on macrophages in different organs, at various developmental stages (immature vs. mature), and across different concentrations (low vs. high).
- To explore potential mechanisms linking Pb-induced macrophage dysfunction to altered health outcomes.
Main Methods:
- Literature review focusing on Pb's effects on macrophage function.
- Analysis of studies examining Pb's impact on phagocytosis, chemotaxis, nitric oxide production, and eicosanoid metabolism in macrophages.
- Inclusion of recent mouse study data on low-dose Pb exposure and its effects on immune cell function.
Main Results:
- Pb exposure decreases macrophage phagocytosis and chemotaxis, and affects nitric oxide and eicosanoid metabolism in mature macrophages.
- In vitro studies show Pb pretreatment increases TNF-α secretion, but in vivo studies indicate decreased intracellular pathogen killing.
- Low, environmentally relevant Pb concentrations can increase erythrocyte phagocytosis and decrease crucial GTPase expression (p65-GBP, p47-IRG) needed for pathogen killing.
Conclusions:
- Pb significantly modulates macrophage function, impacting innate immune defenses.
- Pb-induced alterations in macrophages may involve heme level changes, oxidative stress, and a shift towards Th2 cells and M2 macrophages.
- Understanding Pb's effects on macrophages provides new insights into lead-induced immune compromise and associated health effects.
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