EFFECT OF NONTOXIC MERCURY, ZINC OR CADMIUM PRETREATMENT ON THE CAPACITY OF HUMAN MONOCYTES TO UNDERGO LIPOPOLYSACCHARIDE-INDUCED ACTIVATION

1 Metal salts can inhibit cell activity through direct toxicity to cri tical cellular molecules and structures. On the other hand, they can a lso change cell behaviour by inducing specific genes (including genes encoding members of the metallothionein [MT] gene family). Therefore, transition metals may affect cell functions either by acting as a toxi n, or by transmitting or influencing signals controlling gene expressi on. 2 To explore the latter possibility, we measured the ability of lo w, non-toxic metal pretreatment to alter immune cell behaviour. We pre viously found that pretreatment of human monocytes with zinc induces m etallothionein gene expression and alters their capacity to undergo a bacterial lipopolysaccharide-induced respiratory burst. We showed here that cadmium and mercury salts, at concentrations that exert no disce rnible toxicity, inhibit activation of human monocytic leukemia (THP-1 ) cells. CdCl2 1 mu M, ZnCl2 20-40 mu M or HgCl2 2 mu M pretreatment f or 20 h induced MT-2 mRNA and total MT protein accumulation and had no effect on proliferation potential or metabolic activity, but signific antly inhibited the ability of subsequent lipopolysaccharide treatment to induce the oxidative burst, increased adhesion to plastic, and MT- 2 and interleukin-1 beta (IL-1 beta) mRNA accumulation. 3 The phenomen on of metal-induced suppression of monocyte activation, at metal conce ntrations that have no effect on cell viability, has important implica tions for assessment of acceptable levels of human exposure to cadmium , zinc and mercury.