Blockade of ICAM-1 Improves the Outcome of Polymicrobial Sepsis via Modulating Neutrophil Migration and Reversing Immunosuppression
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 polymicr...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/195290 |
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| author | Yan-jun Zhao Wen-jing Yi Xiao-jian Wan Jun Wang Tian-zhu Tao Jin-bao Li Jia-feng Wang Xiao-ming Deng |
| author_facet | Yan-jun Zhao Wen-jing Yi Xiao-jian Wan Jun Wang Tian-zhu Tao Jin-bao Li Jia-feng Wang Xiao-ming Deng |
| author_sort | Yan-jun Zhao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-39a5abba48e34dc39ceb507d498abfa5 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-39a5abba48e34dc39ceb507d498abfa52025-02-03T01:07:17ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/195290195290Blockade of ICAM-1 Improves the Outcome of Polymicrobial Sepsis via Modulating Neutrophil Migration and Reversing ImmunosuppressionYan-jun Zhao0Wen-jing Yi1Xiao-jian Wan2Jun Wang3Tian-zhu Tao4Jin-bao Li5Jia-feng Wang6Xiao-ming Deng7Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaIntercellular 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.http://dx.doi.org/10.1155/2014/195290 |
| spellingShingle | Yan-jun Zhao Wen-jing Yi Xiao-jian Wan Jun Wang Tian-zhu Tao Jin-bao Li Jia-feng Wang Xiao-ming Deng Blockade of ICAM-1 Improves the Outcome of Polymicrobial Sepsis via Modulating Neutrophil Migration and Reversing Immunosuppression Mediators of Inflammation |
| title | Blockade of ICAM-1 Improves the Outcome of Polymicrobial Sepsis via Modulating Neutrophil Migration and Reversing Immunosuppression |
| title_full | Blockade of ICAM-1 Improves the Outcome of Polymicrobial Sepsis via Modulating Neutrophil Migration and Reversing Immunosuppression |
| title_fullStr | Blockade of ICAM-1 Improves the Outcome of Polymicrobial Sepsis via Modulating Neutrophil Migration and Reversing Immunosuppression |
| title_full_unstemmed | Blockade of ICAM-1 Improves the Outcome of Polymicrobial Sepsis via Modulating Neutrophil Migration and Reversing Immunosuppression |
| title_short | Blockade of ICAM-1 Improves the Outcome of Polymicrobial Sepsis via Modulating Neutrophil Migration and Reversing Immunosuppression |
| title_sort | blockade of icam 1 improves the outcome of polymicrobial sepsis via modulating neutrophil migration and reversing immunosuppression |
| url | http://dx.doi.org/10.1155/2014/195290 |
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