Endocytosis of particulate and soluble IgG immune complexes: differential effects of cytoskeletal modulating agents.

We determined the ability of cytoskeletal modulating agents to affect endocytosis of particulate and soluble immune complexes. Either immunoglobulin G-opsonized 51Cr-labelled erythrocytes (E) or 125I-labelled soluble IgG anti-dinitrophenyl immune complexes (IC) were added to adherent murine peritoneal macrophages and the extent of internalization was measured. Either intracellular 51Cr radioactivity or trichloroacetic acid soluble 125I radioactivity was monitored as an indication of uptake by the cell. In addition to cytochalasin B and colchicine, the phospholipid methylation inhibitors, 3-deazaadenosine and 3-deaza(+/-)aristeromycin, were used. Whereas incubation of macrophages with colchicine alone resulted in 50% inhibition of uptake of E-IgG, there was no effect on the degradation of soluble IC. Both cytochalasin B and colchicine produced a 95% inhibition of E-IgG uptake by macrophages, but these drugs only minimally inhibited (17%) the degradation of soluble immune complexes. Both inhibitors of methylation produced a 50% decrease in phospholipid methylation in treated cells. However, only 3-deazaadenosine inhibited phagocytosis (50% of control for E-IgG and 75% of control for soluble IC). These data suggest that an intact cytoskeleton is necessary for the uptake of a particulate immune complex and much less important for the internalization and degradation of these model soluble immune complexes. In addition, inhibition of phospholipid methylation reactions alone do not impare the uptake and degradation of either a soluble or a particulate immune complex.