Complement and tumor necrosis factor‐α contribute to Mac‐1 (CD11b/CD18) up‐regulation and systemic neutrophil activation during endotoxemia in vivo
Complement and tumor necrosis factor‐α contribute to Mac‐1 (CD11b/CD18) up‐regulation and systemic neutrophil activation during endotoxemia in vivo
复制标题
补体和肿瘤坏死因子-α 有助于体内内毒素血症期间 Mac-1 (CD11b/CD18) 上调和全身中性粒细胞激活
DOI：
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发表时间：
1994
影响因子：
5.5
通讯作者：
H. Jaeschke
中科院分区：
文献类型：
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作者：
R. Witthaut;A. Farhood;C. Smith;H. Jaeschke
在接受5 mg/kg沙门氏菌内毒素处理的雄性Fischer 344大鼠中，使用流式细胞术研究了中性粒细胞上Mac-1（CD 11b/CD 18）粘附糖蛋白表达的增加。在注射内毒素后，观察到Mac-1表达快速且持续增加3倍。用可溶性补体受体1型（sCRl）抑制补体激活完全抑制了Mac-1的初始上调（≤ 15 min），但在后期（30-90 min）并未阻止激活。在此期间，Mac-1表达与血浆中肿瘤坏死因子α（TNF-α）浓度平行增加，并且可以用TNF抗血清显着减弱。为了验证结果，将分离的人中性粒细胞与内毒素注射后不同时间获得的大鼠血浆孵育。使用形状变化作为中性粒细胞活化的指标，补体和TNF-α可被确定为体内内毒素血症期间中性粒细胞活化的负责介质。相比之下，内毒素后肝脏中大量的嗜中性粒细胞积累仅被sCRl轻微减少，并且不受TNF抗血清的影响。可以得出结论，体内内毒素注射后中性粒细胞上的Mac-1上调可能与肝脏中性粒细胞浸润的相关性有限，但可能通过促进粘附依赖性中性粒细胞细胞毒性而对内毒素诱导的肝损伤的发病机制具有重要意义。J. Leukoc. 55：105-111; 1994.
The increased expression of Mac‐1 (CD11b/CD18) adhesion glycoproteins on neutrophils was studied using flow cytometry in male Fischer 344 rats treated with 5 mg/kg Salmonella cnteritidis endotoxin. A rapid and sustained threefold increase of Mac‐1 expression was observed after endotoxin injection. Inhibition of complement activation with the soluble complement receptor type 1 (sCRl) completely suppressed the initial up‐regulation of Mac‐1 (≤ 15 min) but did not prevent the activation during the later phase (30–90 min). During that time period, Mac‐1 expression increased in parallel with the concentration of tumor necrosis factor α (TNF‐α) in plasma and could be significantly attenuated with TNF antiserum. To verify the results, isolated human neutrophils were incubated with rat plasma obtained at various times after endotoxin injection. Using shape change as indicator of neutrophil activation, complement and TNF‐α could be identified as responsible mediators for neutrophil activation during endotoxemia in vivo. In contrast, the massive neutrophil accumulation in the liver after endotoxin was only slightly reduced by sCRl and unaffected by TNF antiserum. It is concluded that Mac‐1 up‐regulation on neutrophils after endotoxin injection in vivo may have limited relevance for hepatic neutrophil infiltration but may be important for the pathogenesis of endotoxin‐induced liver injury by facilitating adherence‐dependent neutrophil cytotoxicity. J. Leukoc. Biol. 55: 105–111; 1994.