Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. I. Suppression of T-cell activation.
Considerable attention has been directed at defining the health deficits associated with exposure to mercurial compounds. While numerous studies have been conducted, the findings have been somewhat contradictory and have led to a confused understanding of the immunotoxicology of mercury. It is becoming clear, however, that the immunotoxic effects of heavy metals in general, and mercury in particular, are dependent upon the assays and source of cells. The major goal of our study was to assess whether low level mercury exposure modulates human T-cell function. Following treatment of T-cells with HgCl2 (0-1000 ng) and MeHgCl (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in T cell proliferation, however, the effect was dependent upon the presence of monocytes. Moreover, in the absence of monocytes, HgCl2 enhance PMA induced T-cell proliferation. MeHgCl was approximately 5-10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize and secrete IL-1. Analysis of the expression of activation markers on the cell surface indicated that one of the earliest markers of lymphocyte activation, CD69, was not effected by mercury. In comparison, T-cell expression of IL-2R and the transferrin receptor was impaired. Of particular interest, cells activated by mitogen for 24 hr became refractory to the immunotoxic effects of mercury. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in T-cell function following exposure to mercury indicates that this metal is immunotoxic at very low exposure levels.
Shenker
B J
BJ
Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia 19104.
Rooney
C
C
Vitale
L
L
Shapiro
I M
IM
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D037181:Lectins, C-Type; D008627:Mercuric Chloride; D008767:Methylmercury Compounds; D000099192:CD69 Antigens; C004925:methylmercuric chloride