title: Effect of lead and arsenic on murine macrophage response.
abstract: Splenic macrophages are highly efficient in trapping and concentrating foreign substances carried in the blood and also the major sites where antibodies are synthesised and from where they are released into the circulation. Lead and Arsenic as environmental agents are considered to be high priority toxic substances largely due to their carcinogenic potentials in humans. However, these heavy metals as carcinogens remain an enigma because while they are definitely active in humans, carcinogenesis in the rodent model has never been convincingly demonstrated. Although macrophages are predominantly recruited to the site of inflammation during inflammatory distress as well as in immune response, nothing is known about the interaction of lead and arsenic with macrophages and their possible role in immunotoxicologic effect. In the present study it is reported that in vivo lead acetate treatment (10 mg/kg body wt) inhibits the cell adhesion property and alters the cell morphology in the splenic macrophages. Results show that there is a significant decrease in alkaline phosphatase release in lead treated macrophages (6.7 +/- 0.88 IU/100 mL) with respect to control (14.17 +/- 0.18). In vivo exposure of sodium arsenite (0.5 mg/kg body wt) also decreases phagocytic activity for ingestion and digestion of exogenous antigens, such as whole microorganism, as evident from the phagocytic index, 11555.55 +/- 62.86 (in control) to 5555.5 +/- 1571.33 in arsenic treated cells. Arsenic exposed cells release 8.15 +/- 0.05 microM nitric oxide, whereas control cells release 10.95 +/- 0.15 microM of nitric oxide, which is also identical following LPS stimulation. Results show that the functional integrity of the target cell is also decreased after arsenic exposure as obtained from the percentage of DNA fragmentation. A greater percentage of DNA fragmentation upon arsenic treatment (43.1 +/- 0.05%) with respect to control (14.9 +/- 0.34%) indicates that arsenic induces apoptosis. In immune cells which are rapidly proliferating and differentiating, inhibition of these heavy metal induced functions may result in similar degree of toxicity and lead to diseased state.
authors.affiliation: Department of Physiology, Immunology Laboratory, Calcutta University, University Colleges of Science and Technology, 92 APC Road, Calcutta 700 009, West Bengal, India.
authors.forename: Mahuya
authors.initials: M
authors.lastname: Sengupta
authors.forename: Biswadev
authors.initials: B
authors.lastname: Bishayi
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D053938:DNA Fragmentation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D010587:Phagocytosis / Q000187:drug effects; D017670:Sodium Compounds / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000473:pathology
chemical_list: D018053:Arsenites; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; D017670:Sodium Compounds; D009569:Nitric Oxide; C017947:sodium arsenite; D000469:Alkaline Phosphatase; C008261:lead acetate