Eppell B A, Newell A M, Brown E J
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1989 Dec 15;143(12):4141-5.
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.
已知吞噬细胞的摄取会因细胞因子和细胞外基质蛋白等生理信号而显著增强，这些信号可能存在于炎症部位。对于在炎症消退过程中可能降低这种吞噬作用增加速率的机制，研究甚少。我们发现，腺苷可作为人外周血单核细胞体外培养来源的巨噬细胞吞噬作用的抑制剂。腺苷（Ado）在抑制IgG Fc和补体介导的吞噬作用方面同样有效。然而，Ado对新鲜分离的单核细胞的吞噬作用没有影响。Ado的抑制作用在培养2天后开始，5天后达到平台期；这种吞噬作用抑制诱导的动力学与巨噬细胞质膜上特异性Ado结合的增加平行。Ado与培养的单核细胞结合的解离常数（Kd）为6微摩尔。这种亲和力以及2-氯腺苷和5'-N-乙基羧酰胺腺苷是最有效的吞噬作用抑制剂这一观察结果表明，单核细胞分化过程中表达的Ado受体属于A2型。吞噬作用的抑制可能由环磷酸腺苷（cAMP）介导，cAMP是几种细胞类型中与A2受体偶联的第二信使。因此，在体外单核细胞分化过程中，A2受体的质膜表达显著增加。这些数据表明，一种潜在的生理介质对单核细胞和巨噬细胞的功能可能有非常不同的影响。这提示了一种机制，即只有当招募新吞噬细胞的信号消退时，炎症部位的吞噬功能才能被下调。
