Extracellular metallothionein effects on lymphocyte activities

Area of Science:

• Immunology
• Toxicology
• Biochemistry

Background:

• Metal cations significantly impact immune responses, leading to either enhanced or suppressed immunological activities.
• Metallothioneins (MTs) are proteins induced by metal cations and are hypothesized to mediate some of these effects.

Purpose of the Study:

• To investigate the role of metallothioneins (MTs) in mediating metal cation influences on the immune response.
• To determine how different metal-MT complexes affect lymphocyte proliferation and immune cell activity.

Main Methods:

• Lymphocyte proliferation assays were conducted using various forms of thioneins (apoprotein, Cd,Zn-MT, Zn-MT, Cd-MT, Hg-MT, Cu-MT).
• Assays included stimulation with mitogens like lipopolysaccharide (LPS) and concanavalin A (ConA), with and without 2-mercaptoethanol.
• Thiol levels and immunoreactivity of different MT preparations were measured.

Main Results:

• Thioneins, including apoproteins and certain metal complexes (Cd,Zn-MT, Zn-MT, Cd-MT), induced lymphocyte proliferation.
• Zn,Cd-MT significantly augmented ConA-induced proliferation, while Hg-MT and Cu-MT inhibited both LPS and ConA-induced proliferation.
• The capacity to induce proliferation correlated with measurable thiol levels, though metal complexation (except Pb) did not substantially alter immunoreactivity.

Conclusions:

• Some metal influences on lymphocytes may occur via a thionein intermediary.
• Certain metal-MT complexes can be detrimental to normal lymphocyte cellular activities, indicating MT does not always act as a protective agent.