Adenosine receptors are expressed during differentiation of monocytes to macrophages in vitro. Implications for regulation of phagocytosis.
Ingestion by phagocytes is known to be markedly enhanced by physiologic signals such as cytokines and extracellular matrix proteins which may be found in inflammatory sites. Little investigation has been made of mechanisms that may depress this increased rate of phagocytosis during resolution of inflammation. We show that adenosine can act as an inhibitor of phagocytosis by macrophages derived from in vitro culture of human peripheral blood monocytes. Adenosine (Ado) is equally effective at inhibiting IgG Fc and complement-mediated phagocytosis. However, Ado has no effect on phagocytosis by freshly isolated monocytes. Inhibition by Ado begins after 2 days in culture and reaches a plateau by 5 days; these kinetics of induction of inhibition of phagocytosis parallel an increase in specific Ado binding to the macrophage plasma membrane. Ado binds to cultured monocytes with a Kd of 6 microM. This affinity and the observation that 2-chloroadenosine and 5'-N-ethylcarboxamidadenosine are the most potent inhibitors of phagocytosis suggest that the Ado receptors expressed during monocyte differentiation are of the A2 type. The inhibition of phagocytosis may be mediated by cAMP, a second messenger coupled to A2 receptors in several cell types. Thus, plasma membrane expression of A2 receptors dramatically increases during monocyte differentiation in vitro. These data show that a potentially physiologic mediator can have very different effects on the function of monocytes and macrophages. This suggests a mechanism whereby phagocytic function at inflammatory sites can be down-regulated if and only if signals for the recruitment of new phagocytes have subsided.
Eppell
B A
BA
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Newell
A M
AM
Brown
E J
EJ
D000241:Adenosine / Q000494:pharmacology; D001667:Binding, Competitive; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D011983:Receptors, Purinergic / Q000502:physiology*
D011983:Receptors, Purinergic; D000242:Cyclic AMP; D000241:Adenosine