Immunomodulating properties of a novel series of protein kinase C activators. The bryostatins.
Low concentrations of the protein kinase C activators, bryostatins 1 and 2 synergized with recombinant B cell stimulatory factor-1 in triggering differentiation (granule enzyme expression) and cytotoxic T lymphocyte (CTL) development in naive, resting lymph node T cells. Bryostatin greatly enhances efficiency of recombinant interleukin-2 in triggering development of in vivo primed CTL during in vitro incubation, thereby providing experimental evidence for the efficacious use of lower concentrations of recombinant interleukin-2 for in vivo tumor rejection studies. Both bryostatins 1 and 2 were able to trigger cytotoxicity of CTL clones against antigen-nonbearing target cells and inhibited CTL cytotoxicity against Ag-specific target cells. Bryostatin 1 and 2 synergize with Ca2+ ionophores in triggering the exocytosis of cytolytic granules from CTL at very low concentrations. In view of the lack of tumor promoting activity of the bryostatins, the possible use of these agents in vivo is discussed.
Trenn
G
G
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Pettit
G R
GR
Takayama
H
H
Hu-Li
J
J
Sitkovsky
M V
MV
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D054713:Bryostatins; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011493:Protein Kinase C / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000276:Adjuvants, Immunologic; D054713:Bryostatins; D007166:Immunosuppressive Agents; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; C054557:bryostatin 2; D011493:Protein Kinase C