Hardart G E, Sullivan G W, Carper H T, Mandell G L
Department of Medicine, University of Virginia, Charlottesville 22908.
Infect Immun. 1991 Mar;59(3):885-9. doi: 10.1128/iai.59.3.885-889.1991.
Adenosine is a natural autocoid and immunomodulator that serves an anti-inflammatory role. Stimulation of polymorphonuclear neutrophils (PMN) with soluble stimuli has been shown to inhibit the PMN oxidative burst. We examined the effects of adenosine and the adenosine analog 2-phenylaminoadenosine (CV-1808) on PMN bactericidal function. Adenosine (10 mM) and CV-1808 (10 to 100 microM) inhibited PMN killing of Staphylococcus aureus. There were more surviving bacteria after 240 min of incubation of PMN with S. aureus and adenosine (10 mM) or CV-1808 (100 microM) (254% +/- 45% and 739% +/- 88% of control, respectively) (P less than 0.05) than there were in the control. In contrast, inosine (10 mM), the major degradation product of adenosine, did not affect killing. Adenosine and CV-1808 did not alter cell association of S. aureus, but S. aureus-activated PMN superoxide release was decreased by adenosine (10 microM) and CV-1808 (10 microM) to 67% +/- 7% and 32% +/- 12% that of the control, respectively (P less than 0.05). Since adenosine inhibited PMN bactericidal function only at approximately 10,000 times peak physiological concentrations, endogenous adenosine levels would not be expected to adversely affect PMN bactericidal function. On the other hand, pharmacological concentrations of adenosine derivatives may decrease the oxidative burst and killing sufficiently to increase host susceptibility to infection.
腺苷是一种天然的自体活性物质和免疫调节剂，具有抗炎作用。已表明用可溶性刺激物刺激多形核中性粒细胞（PMN）可抑制PMN的氧化爆发。我们研究了腺苷和腺苷类似物2-苯氨基腺苷（CV-1808）对PMN杀菌功能的影响。腺苷（10 mM）和CV-1808（10至100 microM）抑制了PMN对金黄色葡萄球菌的杀伤作用。PMN与金黄色葡萄球菌及腺苷（10 mM）或CV-1808（100 microM）孵育240分钟后，存活的细菌比对照组更多（分别为对照组的254%±45%和739%±88%）（P<0.05）。相比之下，腺苷的主要降解产物肌苷（10 mM）不影响杀伤作用。腺苷和CV-1808不改变金黄色葡萄球菌与细胞的结合，但腺苷（10 microM）和CV-1808（10 microM）可使金黄色葡萄球菌激活的PMN超氧化物释放分别降至对照组的67%±7%和32%±12%（P<0.05）。由于腺苷仅在大约生理峰值浓度的10000倍时才抑制PMN杀菌功能，因此预计内源性腺苷水平不会对PMN杀菌功能产生不利影响。另一方面，腺苷衍生物的药理浓度可能会充分降低氧化爆发和杀伤作用，从而增加宿主对感染的易感性。
