Enhancement by cyclic AMP of antibody-induced suppression of the fourth component of complement.
Our laboratory has shown that short-term treatment in vivo or in vitro with monospecific antibody to individual complement components can have long-term effects on the production of those components. In vitro studies have focused on the fourth component of complement (C4) in a guinea pig model. Uniform splenic fragments have been used to mimic the in vivo microenvironment of the C4-producing macrophages. A 4-day exposure to anti-C4 antibody led to a reduction of secreted C4 for 1 to 2 wk and a reduction of intracellular C4 that persisted even longer. In an attempt to understand how short-term exposure to antibody can specifically and permanently disrupt the C4-producing cell, we have determined whether C4 suppression could be enhanced by components that modulate cellular functions through their role as secondary intracellular messengers. We found that compounds which elevated cellular levels of cAMP by any of three mechanisms all enhanced antibody-induced suppression of C4.
M B
MB
Goldman
D S
DS
Becker
K S
KS
O'Rourke
J N
JN
Goldman
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000502:physiology*; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D003181:Complement C4 / Q000096:biosynthesis* / Q000276:immunology; D011415:Complement Factor B / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D006168:Guinea Pigs; D007108:Immune Tolerance / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D000906:Antibodies; D003181:Complement C4; D010726:Phosphodiesterase Inhibitors; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D011415:Complement Factor B; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine