Evaluation of immunotoxic and immunodisruptive effects of inorganic arsenite on human monocytes/macrophages

Int Immunopharmacol. 2004 Dec 15;4(13):1661-73. doi: 10.1016/j.intimp.2004.07.027.

Abstract

A trivalent inorganic arsenic, arsenite, has been causing chronic inflammation in humans through the consumption of contaminated well water. The total peripheral blood arsenic concentrations of chronic arsenic-exposed patients, who had inflammatory-like immune responses, are less than 1 microM, thus, nM concentrations may be very important regarding the chronic inflammatory effects by arsenite. However, there are few reports about the biological effects of low concentrations of arsenite in mammalian cells, especially in normal immune effector cells. In this study, we examined whether arsenite has any biological and/or toxicological effects on the differentiation of human peripheral blood monocytes into macrophages using the colony-stimulating factor (CSF) in vitro compared with that of other metallic compounds, and found that arsenite sensitively inhibited the CSF-induced in vitro maturation of monocytes into macrophages at nM levels, and it also induced small, nonadhesive and CD14-positive abnormal macrophage generation from monocytes with granulocyte-macrophage CSF (GM-CSF) at 50-500 nM without cell death. The addition of other metallic compounds, including chromium, selenium, mercury, cadmium, nickel, copper, zinc, cobalt, manganese and other human pentavalent arsenic metabolites, such as inorganic arsenate, monomethylarsonic acid and dimethylarsinic acid, could not induce the same abnormal cell generation from monocytes with CSFs at any concentration and any additional time schedules; they showed only simple cytolethality in monocytes and macrophages at n-mM levels accompanied by cell death. This work may have implications in the arsenic-induced chronic inflammation in humans.

Publication types

  • Comparative Study

MeSH terms

  • Arsenates / adverse effects
  • Arsenates / immunology
  • Arsenites / adverse effects*
  • Arsenites / immunology*
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Environmental Pollutants / adverse effects
  • Environmental Pollutants / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • HL-60 Cells
  • Humans
  • Immunotoxins / adverse effects*
  • Immunotoxins / chemistry
  • Immunotoxins / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Macrophage Colony-Stimulating Factor / immunology
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophages / drug effects*
  • Macrophages / pathology
  • Macrophages / physiology
  • Monocytes / drug effects*
  • Monocytes / pathology
  • Monocytes / physiology
  • Sodium Compounds / adverse effects*
  • Sodium Compounds / immunology*
  • Toxicity Tests / methods

Substances

  • Arsenates
  • Arsenites
  • Environmental Pollutants
  • Immunotoxins
  • Lipopolysaccharide Receptors
  • Sodium Compounds
  • sodium arsenite
  • Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor