Exogenous cyclic AMP, cholera toxin, and endotoxin induce expression of the lipopolysaccharide receptor CD14 in murine bone marrow cells: role of purinoreceptors.
Little is known about the mechanisms of lipopolysaccharide (LPS) signaling in immature cells that do not express the LPS receptor CD14 yet. Bone marrow granulocytes do not constitutively express CD14 but can be stimulated by low doses of LPS in the absence of serum and then express an inducible form of LPS receptor (iLpsR). We show that in addition to LPS, cholera toxin (CT) and various cyclic AMP (cAMP) analogs can also induce the expression of iLpsR, which was identified as CD14. Induction was independent of intracellular cAMP. The hypothesis that cAMP analogs act via a cell surface receptor was suggested by the unresponsiveness of trypsin-treated cells to these inducers and by the specific binding of [(3)H]cAMP to the cells. This binding was not inhibited by LPS or CT but was inhibited by various purine derivatives. However, the receptor involved is not a conventional purinoreceptor since both an agonist and an antagonist of such receptors were able to induce iLpsR expression. The results suggest that cAMP analogs and other purine derivatives induce iLpsR after interaction with an unconventional, trypsin-sensitive, purinoreceptor distinct from LPS and CT receptors.
Pedron
T
T
Molecular Immunophysiology Unit, URA-1961, National Center for Scientific Research, Pasteur Institute, Paris, France.
Girard
R
R
Chaby
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D001854:Bone Marrow Cells / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000276:immunology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000276:immunology; D013873:Thionucleotides / Q000494:pharmacology*; D014316:Tritium; D014357:Trypsin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D011983:Receptors, Purinergic; D013873:Thionucleotides; D014316:Tritium; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D014357:Trypsin; D015056:1-Methyl-3-isobutylxanthine