Mitogenic effects of beryllium and zirconium salts on mouse splenocytes in vitro

The beryllium (Be) and zirconium (Zr) salts, BeSO4 and Zr(SO4)2, each exerted a concentration-dependent stimulation of mouse spleen cell proliferation as measured by an increase in [3H]thymidine incorporation into lymphocyte DNA, although the maximal response induced by Zr(SO4)4 (4-5 fold at 100-200 microM) was greater than that by BeSO4 (2-3 fold at 1-5 microM). Preincubation of splenocytes with low concentrations of BeSO4 (less than 1 microM) or a broad range of Zr(SO4)2 concentrations (2-100 microM) was also found to assist subsequent lectin (concanavalin A; ConA)-mediated lymphocyte proliferation. The results indicate that at defined concentrations Be and Zr salts can both act as lymphocyte mitogens and augment the functional responsiveness of immune cells, which may help explain the characteristic induction of delayed hypersensitivity and production of immunological granulomas by these metals in vivo.