Studies of the mechanism of tunicamycin in hibition of IgA and IgE secretion by plasma cells.
Tunicamycin, an antibiotic which blocks the formation of N-acetylglucosamine-lipid intermediates, thereby preventing glycosylation of glycoproteins, inhibits the secretion of IgA and IgE by MOPC 315 mouse plasma cells and IR162 rat plasma cells, respectively. At 0.5 microng of tunicamycin per ml, D-[14C]glucosamine incorporation into newly synthesized immunoglobulin was inhibited greater than 90% while the overall rate of protein synthesized was much less inhibited (40% in the case of MOPC 315 cells and 13% in the case of IR162 cells). This dose of tunicamycin produced an 85% inhibition of IgA secretion by the MOPC 315 cells and a complete inhibition of intact IgE secretion by the IR162 plasma cells. In contrast, tunicamycin had little effect on the secretion of normally nonglycosylated lambda light chains or on cell-free protein synthesis, demonstrating that tunicamycin is not a general inhibitor of protein synthesis or a non-specific inhibitor of protein secretion. No enhancement of intracellular degradation of nonglycosylated immunoglobulin could be demonstrated. Electron microscopy of tunicamycin-treated MOPC 315 cells revealed marked dilatations of the rough endoplasmic reticulum, and direct immunofluorescence indicated that the dilated rought endoplasmic reticulum contained IgA. These data indicate that glycosylation of newly synthesized IgA and IgE may be necessary for normal secretion to occur.
D000117:Acetylglucosamine / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007070:Immunoglobulin A / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010950:Plasma Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010954:Plasmacytoma / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007070:Immunoglobulin A; D009363:Neoplasm Proteins; D007073:Immunoglobulin E; D005944:Glucosamine; D000117:Acetylglucosamine