Macrophage adherence prevents apoptosis induced by ricin.
Ricin, a lectin with potent protein synthesis inhibitory properties, has been known to cause morphological changes in epithelial cells typical of apoptosis (P. Waring et al., Med. Res. Rev. 11, 1-17 (1991)). In earlier preliminary experiments from this laboratory with murine macrophages and T-blasts (P. Waring, J. Biol. Chem. 265, 14,476-14,480 (1990)), it was shown that ricin induces regular DNA fragmentation, a biochemical event also associated with apoptosis. Here we confirm morphologically and by examination of DNA fragmentation that macrophages undergo apoptosis when treated with ricin in a dose-dependent manner. Ricin also inhibits adherence of macrophages to plastic surfaces but does not affect adherence of preadhered macrophages after 7 h of treatment. We also report that adherence significantly diminishes DNA fragmentation induced in macrophages by ricin but has no effect on ricin-induced inhibition of protein synthesis. From these results we may conclude that the property of ricin to induce apoptosis may not be related to its ability to inhibit protein synthesis in macrophages. Moreover, the anti-phagocytic activity of ricin may be a direct consequence of its ability to fragment DNA and induce apoptosis and not of its ability to inhibit protein synthesis. We also observed no immediate increase in Ca2+ concentration when macrophages were treated with ricin indicating that ricin-induced apoptosis may not involve the activation of a Ca2+ dependent endonuclease(s).
Khan
T
T
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Waring
P
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D008264:Macrophages / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011506:Proteins / Q000378:metabolism; D012276:Ricin / Q000494:pharmacology*; D013997:Time Factors
D011506:Proteins; D004247:DNA; D012276:Ricin; D002118:Calcium