Blockade of ICAM-1 improves the outcome of polymicrobial sepsis via modulating neutrophil migration and reversing immunosuppression.
Blockade of ICAM-1 improves the outcome of polymicrobial sepsis via modulating neutrophil migration and reversing immunosuppression.
复制标题
阻断 ICAM-1 通过调节中性粒细胞迁移和逆转免疫抑制改善多种微生物败血症的结果
DOI：
10.1155/2014/195290
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发表时间：
2014
影响因子：
4.6
通讯作者：
Deng XM
中科院分区：
文献类型：
--
作者：
Zhao YJ;Yi WJ;Wan XJ;Wang J;Tao TZ;Li JB;Wang JF;Deng XM
细胞间粘附分子-1 （ICAM-1）是脓毒症中介导中性粒细胞迁移和浸润的关键粘附分子。但它在败血症结果中的作用仍然是矛盾的。本研究旨在探讨抗icam -1抗体在多微生物脓毒症和脓毒症诱导的免疫紊乱中的作用。通过生存分析、细菌清除率和肺损伤评估抗icam -1抗体对盲肠结扎穿刺（CLP）脓毒症结局的影响。研究了其对胸腺和脾脏中性粒细胞迁移和浸润以及淋巴细胞状态的影响。结果表明，ICAM-1 mRNA在CLP小鼠的肺、胸腺和脾脏中表达上调。抗icam -1抗体提高了CLP小鼠的存活率和细菌清除率，减轻了肺损伤。中性粒细胞向腹腔的迁移增强，而向肺、胸腺和脾脏的浸润被ICAM-1阻断。抗icam -1抗体对败血症诱导的胸腺和脾脏细胞凋亡也有抑制作用。正向共刺激分子包括CD28、CD80和CD86上调，而负向共刺激分子包括PD-1和PD-L1下调。总之，ICAM-1阻断可改善脓毒症的预后。其原理可能包括中性粒细胞迁移的调节和免疫抑制的逆转。
Intercellular adhesion molecule-1 (ICAM-1) is a key adhesion molecule mediating neutrophil migration and infiltration during sepsis. But its role in the outcome of sepsis remains contradictory. The current study was performed to investigate the role of anti-ICAM-1 antibody in the outcome of polymicrobial sepsis and sepsis-induced immune disturbance. Effect of anti-ICAM-1 antibody on outcome of sepsis induced by cecal ligation and puncture (CLP) was evaluated by the survival analysis, bacterial clearance, and lung injury. Its influence on neutrophil migration and infiltration, as well as lymphocyte status, in thymus and spleen was also investigated. The results demonstrated that ICAM-1 mRNA was upregulated in lung, thymus, and spleen of CLP mice. Anti-ICAM-1 antibody improved survival and bacterial clearance in CLP mice and attenuated lung injury. Migration of neutrophils to peritoneal cavity was enhanced while their infiltration into lung, thymus, and spleen was hampered by ICAM-1 blockade. Anti-ICAM-1 antibody also prevented sepsis-induced apoptosis in thymus and spleen. Positive costimulatory molecules including CD28, CD80, and CD86 were upregulated, while negative costimulatory molecules including PD-1 and PD-L1 were downregulated following anti-ICAM-1 antibody administration. In conclusion, ICAM-1 blockade may improve outcome of sepsis. The rationale may include the modulated neutrophil migration and the reversed immunosuppression.
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影响因子：
1.2
作者：
Treacher, DF;Sabbato, M;Gant, V
通讯作者：
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