MACROPHAGE ADHERENCE PREVENTS APOPTOSIS INDUCED BY RICIN

Ricin, a lectin with potent protein synthesis inhibitory properties, h as been known to cause morphological changes in epithelial cells typic al of apoptosis (P. Waring et al., Med. Res. Rev. 11, 1-17 (1991)). In earlier preliminary experiments from this laboratory with murine macr ophages and T-blasts (P. Waring, J. Biol. Chem. 265, 14476-14480 (1990 )), it was shown that ricin induces regular DNA fragmentation, a bioch emical event also associated with apoptosis. Here we confirm morpholog ically and by examination of DNA fragmentation that macrophages underg o apoptosis when treated with ricin in a dose-dependent manner. Ricin also inhibits adherence of macrophages to plastic surfaces but does no t affect adherence of preadhered macrophages after 7 h of treatment. W e also report that adherence significantly diminishes DNA fragmentatio n induced in macrophages by ricin but has no effect on ricin-induced i nhibition of protein synthesis. From these results we may conclude tha t the property of ricin to induce apoptosis may not be related to its ability to inhibit protein synthesis in macrophages. Moreover, the ant i-phagocytic activity of ricin may be a direct consequence of its abil ity to fragment DNA and induce apoptosis and not of its ability to inh ibit protein synthesis. We also observed no immediate increase in Ca2 concentration when macrophages were treated with ricin indicating tha t ricin-induced apoptosis may not involve the activation of a Ca2+ dep endent endonuclease(s).