Contract Grant Sponsor: NIH.
Lead Modulation of Macrophages Causes Multiorgan Detrimental Health Effects
Article first published online: 27 MAY 2014
© 2014 Wiley Periodicals, Inc.
Journal of Biochemical and Molecular Toxicology
Volume 28, Issue 8, pages 355–372, August 2014
How to Cite
Kasten-Jolly, J. and Lawrence, D. A. (2014), Lead Modulation of Macrophages Causes Multiorgan Detrimental Health Effects. J. Biochem. Mol. Toxicol., 28: 355–372. doi: 10.1002/jbt.21572
Contract Grant Numbers: ES03179 and ES013857.
- Issue published online: 4 AUG 2014
- Article first published online: 27 MAY 2014
- Manuscript Accepted: 30 APR 2014
- Manuscript Revised: 17 APR 2014
- Manuscript Received: 29 JAN 2014
- NIH. Grant Numbers: ES03179, ES013857
- Nitric Oxide;
- Nitric Oxide Synthase;
- Oxidative Stress;
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.