Nakagawara A, DeSantis N M, Nogueira N, Nathan C F
J Clin Invest. 1982 Nov;70(5):1042-8. doi: 10.1172/jci110691.
Supernatants from mitogen- or antigen-stimulated human blood mononuclear cells enhanced the capacity of human monocytes or monocyte-derived macrophages (MDM) to release H(2)O(2) or O(2) in response to phorbol myristate acetate or zymosan. The stimulatory effect of lymphokines (LK) lasted approximately 5 d, regardless of the time of their addition. However, the magnitude of stimulation depended on whether LK were added to freshly explanted monocytes or to MDM. When LK were added on day 0 of culture, they enhanced MDM H(2)O(2)-releasing capacity approximately 40% measured on day 3, when H(2)O(2)-releasing capacity in the controls was maximal. Addition of LK on day 2 retarded the decline in H(2)O(2)-releasing capacity normally seen by day 5, so that LK-treated cells released about twice as much H(2)O(2) as the controls. Addition of LK to MDM that had already lost most of their H(2)O(2)-releasing capacity (e.g., on day 4-6) restored it to an average of 60% of the values seen with freshly explanted monocytes. In this case, LK-treated cells were about 12 times more active than cells incubated in medium alone. The effects of LK were dose- and time-dependent, with maximal effects requiring 3 d of exposure. The specific activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and myeloperoxidase, and the specific content of glutathione were not diminished in LK-treated MDM, suggesting that increased synthesis of H(2)O(2) rather than decreased catabolism probably explained the greater release of H(2)O(2) from LK-treated cells. In contrast, release of H(2)O(2) was suppressed 93+/-4% by exposing monocytes for 4 d to hydrocortisone (50%-inhibitory concentration, 1.9+/-0.3 x 10(-7) M). Thus, the oxidative metabolism of human mononuclear phagocytes can be markedly modulated in vitro: augmented by mediators released from lymphocytes during an immune response, and suppressed by antiinflammatory corticosteroids.
丝裂原或抗原刺激的人血单核细胞的上清液增强了人单核细胞或单核细胞衍生的巨噬细胞（MDM）对佛波酯肉豆蔻酸酯或酵母聚糖作出反应释放H₂O₂或O₂的能力。淋巴细胞因子（LK）的刺激作用持续约5天，与添加时间无关。然而，刺激的程度取决于LK是添加到刚分离出的单核细胞还是MDM中。当在培养第0天添加LK时，在第3天测量，它们使MDM释放H₂O₂的能力增强了约40%，此时对照中H₂O₂释放能力达到最大值。在第2天添加LK减缓了通常在第5天出现的H₂O₂释放能力的下降，因此经LK处理的细胞释放的H₂O₂约为对照的两倍。将LK添加到已经失去大部分H₂O₂释放能力的MDM中（例如在第4 - 6天），可将其恢复到刚分离出的单核细胞所观察到的值的平均60%。在这种情况下，经LK处理的细胞比仅在培养基中培养的细胞活性高约12倍。LK的作用呈剂量和时间依赖性，最大作用需要3天的暴露时间。在经LK处理的MDM中，超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和髓过氧化物酶的比活性以及谷胱甘肽的比含量并未降低，这表明H₂O₂释放增加可能是由于合成增加而非分解代谢减少所致。相反，将单核细胞暴露于氢化可的松（50%抑制浓度，1.9±0.3×10⁻⁷M）4天，H₂O₂释放被抑制93±4%。因此，人单核吞噬细胞的氧化代谢在体外可被显著调节：在免疫反应期间被淋巴细胞释放的介质增强，被抗炎皮质类固醇抑制。
