Extracellular metallothionein effects on lymphocyte activities

Abstract

Metal cation influences on the immune response have been reported in a wide variety of experimental systems. These influences can either result in the augmentation or suppression of immuno-logical activities. In order to investigate possible mechanisms of these influences, we examined the role that a metal cation-induced protein, metallothionein (MT), might play. Our findings suggest that thioneins, either as apoproteins or when complexed as Cd,ZnMT, ZnMT, or CdMT, are capable of inducing lymphocyte proliferation. This level of induction is substantially reduced when Zn,CdMT is added to lymphocyte cultures in the presence of 50 μM 2-mercaptoethanol. Apoprotein, Zn,CdMT, ZnMT and CdMT also augment LPS-induced proliferation of splenic lymphocytes. Only the Zn,CdMT preparation significantly augmented ConA-induced proliferation. HgMT and CuMT were inhibitory as additions in either LPS or ConA mitogen proliferation assays, and did not stimulate proliferation when added alone to lymphocyte cultures. The capacity to induce proliferation correlates with the measurable thiol level of the particular thionein. Interestingly, Zn,CdMT and apothionein had an equivalent number of accessible thiols. Although Zn, Pb, Hg and Cu lowered the number of these sites, the immunoreactivity of these MTs was not altered substantially except by Pb. These results suggest that some metal influences on lymphocytes might be through a thionein intermediary. Our results also demonstrate that thioneins complexed with certain metal cations are detrimental to the normal cellular activities of lymphocytes. At least in these circumstances, MT does not play a role as a protective agent.