Cardiac toxicity of arsenic trioxide

tion of Karpas 299 cells with immobilized antibodies to CD30 was found to potently induce cell death, whereas in the same experiment the addition of these antibodies in their soluble form did not induce cell death and actually slightly enhanced viability (Figure 1). Also noteworthy is the fact that, in the earlier report by Gruss et al4 in which the cytotoxic effects of M44 and M67 were originally described, plate-bound antibodies were used. In preliminary experiments using plate-bound HeFi-1, we have also observed a proapoptotic effect (data not shown). In summary, we suggest that apparently different experimental methods are the most likely explanation for the discrepancies between our report and that of Levi et al, in particular the use of immobilized antibody versus plate-bound antibody. The different effects of soluble and immobilized antibody are suggestive of an intriguing physiologic mechanism by which low levels of CD30 activation may induce cell-cycle arrest, activation of NF-kB, and the concomitant induction of antiapoptotic genes, whereas a stronger CD30-activation signal may result in a transient and more limited activation of NF-kB and ultimately cell death. The strength of the CD30 signal may be determined by numerous factors, including the density of CD30 receptors on the cell and the form of ligand (ie, membrane-bound or soluble). The threshold sensitivity of a given cell may also be determined by additional factors, such as the stability of intracellular signaling intermediates, particularly TRAF2. Thus, the apparent discrepancies between our data and those of Levi et al may reflect a novel physiologic function of CD30.