Requirement for endocytosis of poly(rI).poly(rC) to generate toxicity on interferon-treated LM cells.
Poly(rI).poly(rC) induces a lytic reaction in interferon-treated mouse LM cells. We have attempted to determine whether the intracellular penetration of poly(rI).poly(rC) is a prerequisite for cell lysis and to gain some insight into the pathway followed. We found that poly(rI).poly(rC) coupled to Sepharose beads was unable to generate lysis of interferon-treated cells whereas the cells underwent lysis after microinjection of poly(rI).poly(rC). Some inhibitors of endocytosis were found to inhibit the development of the lytic reaction. Lysosomotropic amines or a low temperature (19 degrees C) blocked endocytosis of poly(rI).poly(rC) but did not prevent its uptake. The internalization of poly(rI).poly(rC) was energy-dependent and was blocked when sodium azide and 2-deoxyglucose were added simultaneously. We conclude that poly(rI).poly(rC) is internalized and reaches an acidic compartment before triggering the lytic reaction in the cell.
D000588:Amines / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D007372:Interferons / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008845:Microinjections; D011070:Poly I-C / Q000378:metabolism* / Q000494:pharmacology; D011107:Polylysine / Q000008:administration & dosage; D011796:Quinacrine / Q000494:pharmacology; D012685:Sepharose / Q000008:administration & dosage; D013696:Temperature
D000588:Amines; D011107:Polylysine; D007372:Interferons; D012685:Sepharose; D011796:Quinacrine; D011070:Poly I-C