Effects of low concentrations of cadmium on immunoglobulin E production by human B lymphocytes in vitro.
Exposure to cadmium (Cd) can cause a variety of biological effects including alterations of immune responses in animals and humans. Both immunosuppression and immunoenhancement have been reported. The present study was aimed at investigating the consequences of exposure to Cd on the human immunoglobulin (Ig) E synthesis, using purified peripheral blood B lymphocytes and IL-4 and anti-human CD40 monoclonal antibody (a-CD40 mAb) as stimuli. Low concentrations of Cd (0.1-10 microM) markedly inhibited production of IgE in a concentration-dependent manner. IgG production, in contrast to IgE, showed a tendency towards being enhanced by Cd, although with a certain individual variability; IgM production was not affected. Cd failed to alter immediate surface expression of the activation markers CD69 and CD23 indicating that early activation events were not impaired. However, the portion of activated B cells was diminished by Cd after stimulation for more than 24 h, paralleled by a concomitant decrease in viability and a subsequent reduction in proliferation. These data suggest that the mechanism of Cd action on activated B cells involved pathways that interrupted an effectively initiated cell activation and induced a cytotoxic signal. Results from this study thus provide further evidence for and new information on the immunotoxic and immunomodulatory effects of Cd on human immune responses.
Institute of Hygiene, University of Graz, Universitaetsplatz 4, A-8010, Graz, Austria. sandra.jelovcan@kfunigraz.ac.at
Sandra
S
Jelovcan
Andrea
A
Gutschi
Barbara
B
Kleinhappl
Peter
P
Sedlmayr
Sonja
S
Barth
Egon
E
Marth
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology; D002104:Cadmium / Q000633:toxicity*; D002470:Cell Survival / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017455:Receptors, IgE / Q000096:biosynthesis / Q000276:immunology; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens; D002104:Cadmium; D007073:Immunoglobulin E; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015847:Interleukin-4; D037181:Lectins, C-Type; D017455:Receptors, IgE; D000099192:CD69 Antigens