PORTAL ENDOTOXEMIA STIMULATES THE RELEASE OF AN IMMUNOSUPPRESSIVE FACTOR FROM ALVEOLAR AND SPLENIC MACROPHAGES
PORTAL ENDOTOXEMIA STIMULATES THE RELEASE OF AN IMMUNOSUPPRESSIVE FACTOR FROM ALVEOLAR AND SPLENIC MACROPHAGES
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DOI：
10.1006/jsre.1993.1102
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发表时间：
1993-07-01
影响因子：
2.2
通讯作者：
SHEINER, PA
中科院分区：
文献类型：
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作者：
MARSHALL, JC;RIBEIRO, MB;SHEINER, PA
细胞介导的免疫功能受损既是危重疾病的常见表现，也是传染病发病率和死亡率增加的潜在原因。引起全身免疫调节改变的机制尚不完全清楚；然而，单核细胞和固定组织巨噬细胞似乎起着核心作用。我们之前已经证明，将革兰氏阴性菌输注到门静脉，而不是输注到体循环中，可诱导体内延迟性超敏反应性和体外有丝分裂原刺激的淋巴细胞增殖的抑制。目前的研究是为了探讨这种抑制的机制。大鼠经下腔静脉或门静脉注射杀灭3 × 108只铜绿假单胞菌；24小时后处死，观察分离脾细胞分裂原驱动的增殖反应。门脉输注显著抑制Con a诱导的增殖反应（15.5±2.7 cpm × 10-3，相比之下，肝下静脉腔静脉输注动物为68.6±9.8 cpm × 10-3，未手术对照组为48.0±5.4 cpm × 10-3）。抑制被证明是一种可溶性抑制因子从脾贴壁细胞释放的结果。腹腔注射动物肺泡巨噬细胞培养上清中存在的可溶性因子也可诱导对照淋巴细胞增殖反应的抑制（腹腔注射动物为4.7±0.4 cpm × 10-3vs 88.6±27 cpm × 10-3，非手术对照组为60.1±8.4 cpm × 10-3）。刺激这种因子释放的不是内毒素，而是肝脏释放的第二种因子。这些结果表明，门脉内毒素血症可以诱导全身免疫抑制，并提示了危重疾病免疫改变启动的新机制。
Impairment of cell-mediated immunity is both a common manifestation of critical illness and a potential cause of increased infectious morbidity and mortality. The mechanisms responsible for alterations in systemic immune regulation are incompletely understood; however, monocytes and fixed tissue macrophages appear to play a central role. We have previously shown that infusion of gram-negative organisms into the portal vein, but not into the systemic circulation, induces suppression of delayed hypersensitivity responsivenessin vivoand of mitogen-stimulated lymphocyte proliferationin vitro. The present studies were undertaken to probe the mechanisms of this suppression. Rats received 3 × 108killedPseudomonas aeruginosavia the inferior vena cava or the portal vein; they were sacrificed 24 hr later and the mitogen-driven proliferative responses of isolated splenocytes were assayed. Portal infusion resulted in significant suppression of Con A-induced proliferative responses (15.5 ± 2.7 cpm × 10-3compared to 68.6 ± 9.8 cpm × 10-3for infrahepatic vena caVA-infused animals and 48.0 ± 5.4 cpm × 10-3for nonoperated controls). Suppression was shown to be a consequence of the release of a soluble suppressive factor from splenic adherent cells. Suppression of the proliferative responses of control lymphocytes could also be induced by a soluble factor present in culture supernatants of alveolar macrophages harvested from portally infused animals (4.7 ± 0.4 cpm × 10-3vs 88.6 ± 27 cpm × 10-3for systemically infused animals and 60.1 ± 8.4 cpm × 10-3for nonoperated controls). The stimulus for the release of this factor was not endotoxin, but a second factor released from the liver. These results demonstrate that portal endotoxemia can induce systemic immune suppression and suggest a novel mechanism for the initiation of the immunologic alterations of critical illness.