Loss of response to beta-adrenoceptor agonists during the maturation of human monocytes to macrophages in vitro.
We have previously reported that human airway macrophages do not respond to the beta-adrenoceptor agonist isoprenaline. The airway macrophage is known to be derived from the blood monocyte. In this study we have assessed the effect of beta-adrenoceptor stimulation on human monocytes matured into macrophages in vitro, to determine whether the lack of response previously observed in the airway macrophage may be a consequence of differentiation. The release of thromboxane B2 (TXB2) from freshly isolated monocytes stimulated by opsonized zymosan (OPZ) was inhibited by 39.3 +/- 5.5% in the presence of isoprenaline (10(-7) M). However, the response was lost in the monocyte-derived macrophage (MDM), where isoprenaline (10(-7) M) caused only 4.0 +/- 9.3% inhibition of OPZ-stimulated TXB2 release. In contrast forskolin (10(-5) M) inhibited MDM TXB2 release by 36.4 +/- 17.3%, indicating that the adenylyl cyclase was functional. Measurement of adenylyl cyclase activity showed that there was a reduction in the basal level, 17.03 +/- 4.1 to 7.9 +/- 4.6 cyclic AMP pmol/min/mg protein, and NaF (10(-2) M)-induced activity, 116.3 +/- 32.1 to 21.9 +/- 12.6 cyclic AMP pmol/min/mg protein, between freshly isolated monocytes and MDMs, respectively. In addition, there was no change in MDM basal adenylyl cyclase activity on exposure to isoprenaline. Thus we have demonstrated the loss of beta-adrenoceptor function during the maturation of human monocytes to macrophages in vitro, despite a functional adenylyl cyclase system. In this respect the monocyte-derived macrophage is like the airway macrophage.
Baker
A J
AJ
Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Fuller
R W
RW
D000118:Acetylglucosaminidase / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D002454:Cell Differentiation; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction; D012969:Sodium Fluoride / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D013929:Thromboxane B2; D012969:Sodium Fluoride; D015054:Zymosan; D000118:Acetylglucosaminidase; D000262:Adenylyl Cyclases; D007545:Isoproterenol