Modulation of lymphocyte proliferation and immunoglobulin production by transferrin-gallium.
Gallium resembles iron with respect to transferrin (Tf) binding and cellular uptake via Tf receptors. We have previously shown that transferrin-gallium (Tf-Ga) complexes interfere with the cellular incorporation of iron and inhibit the proliferation of HL60 cells. Since mitogen-stimulated peripheral blood lymphocytes express Tf receptors, we examined the effect of Tf-Ga on lymphocyte proliferation and on immunoglobulin synthesis by B-lymphocytes. Tf-Ga inhibited phytohemagglutinin, pokeweed mitogen, and tetanus toxoid-stimulated lymphocyte proliferation by greater than 50%, an effect which appeared to be cytostatic rather than cytotoxic. In cocultures of T-lymphocytes or CD4+ T-lymphocytes and B-lymphocytes, Tf-Ga also inhibited pokeweed mitogen-stimulated immunoglobulin production by 84 to 100%. Tf-Ga inhibited both T-independent Epstein Barr virus-stimulated B-lymphocyte proliferation and immunoglobulin production; however, these effects appeared to be independent of each other, since immunoglobulin production was inhibited by 75% by a concentration of Tf-Ga which did not uniformly inhibit proliferation. Tf-Ga is capable of targeting Tf receptor-bearing T- and B-lymphocytes and interfering with their proliferation and function. Such effects may be of relevance to patients being treated with this metal. The potential immunosuppressive activity of gallium warrants further investigation.
Chitambar
C R
CR
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Seigneuret
M C
MC
Matthaeus
W G
WG
Lum
L G
LG
D005708:Gallium / Q000494:pharmacology*; D004854:Herpesvirus 4, Human; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000032:analysis; D014168:Transferrin / Q000494:pharmacology*
D007136:Immunoglobulins; D008934:Mitogens; D011990:Receptors, Transferrin; D014168:Transferrin; D005708:Gallium