Effect of cyclic adenosine monophosphate, 5'-(N-ethylcarboxyamido)-adenosine and methylxanthines on the release of thromboxane and lysosomal enzymes from human alveolar macrophages and peripheral blood monocytes in vitro.
We have investigated the effect of the manipulation of intracellular cyclic adenosine monophosphate (cyclic AMP) and the stimulation of adenosine receptors on the function of human alveolar macrophages in vitro. Human alveolar macrophages harvested by bronchoalveolar lavage were stimulated by opsonised zymosan 1 mg/ml in the presence of N6,2'0-dibutyryladenosine 3':5' cyclic monophosphate (dibutyryl cyclic AMP) 5 x 10(-6) to 5 x 10(-3) M,8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo cyclic AMP) 5 x 10(-6) to 5 x 10(-3) M, 5'-(N-ethylcarboxamido)-adenosine (NECA) 10(-7) to 10(-4) M, adenosine 10(-7) to 10(-4) M, theophylline 5 x 10(-6) to 5 x 10(-3) M and enprofylline 5 x 10(-8) to 5 x 10(-4) M. The subsequent release of thromboxane B2 (TXB2) and N-acetyl-beta-D-glucosaminidase (NAG) activity was monitored. In addition, the release of TXB2 and NAG from zymosan stimulated human monocytes incubated in the presence of NECA 10(-7) to 10(-4) M was measured. The TXB2 release from alveolar macrophages were inhibited by dibutyryl cyclic AMP and 8-bromo cyclic AMP and to a lesser extent by NECA, theophylline and enprofylline. However, adenosine had no effect. None of the agents studied altered NAG release. In addition, monocytes showed greater sensitivity to the inhibitory effects of 5-N-ethylcarboxamido adenosine than alveolar macrophages. In conclusion, the alveolar macrophage was inhibited by stable analogues of cyclic AMP and xanthines at supratherapeutic concentrations but have no functional excitatory adenosine receptors and only a residual inhibitory adenosine receptor function compared to the precursor monocyte.
Baker
A J
AJ
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, U.K.
Fuller
R W
RW
D000118:Acetylglucosaminidase / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
D013931:Thromboxanes; D014970:Xanthines; D019830:Adenosine-5'-(N-ethylcarboxamide); D013929:Thromboxane B2; D015054:Zymosan; D000242:Cyclic AMP; D000118:Acetylglucosaminidase; D000262:Adenylyl Cyclases; D000241:Adenosine