scholarly journals Blockade of ICAM-1 Improves the Outcome of Polymicrobial Sepsis via Modulating Neutrophil Migration and Reversing Immunosuppression

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yan-jun Zhao ◽  
Wen-jing Yi ◽  
Xiao-jian Wan ◽  
Jun Wang ◽  
Tian-zhu Tao ◽  
...  
Keyword(s):  
Lung Injury ◽  
Adhesion Molecule ◽  
Neutrophil Migration ◽  
Cecal Ligation ◽  
Costimulatory Molecules ◽  
Polymicrobial Sepsis ◽  
Intercellular Adhesion Molecule ◽  
Bacterial Clearance ◽  
Intercellular Adhesion Molecule 1 ◽  
Induced Apoptosis

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.

scholarly journals Dietary fish oil enhances adhesion molecule and interleukin-6 expression in mice with polymicrobial sepsis

2006 ◽  
Vol 96 (5) ◽  
pp. 854-860 ◽  
Author(s):  
Chun-Sen Hsu ◽  
Wan-Chun Chiu ◽  
Chiu-Li Yeh ◽  
Yu-Chen Hou ◽  
Szu-Yuan Chou ◽  
...  
Keyword(s):  
Fish Oil ◽  
Adhesion Molecule ◽  
Neutrophil Infiltration ◽  
Interferon Γ ◽  
Polymicrobial Sepsis ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Intercellular Adhesion Molecule 1 ◽  
Group 12 ◽  
Dietary Fish

This study investigated the effects of fish oil (FO) diet on plasma intercellular adhesion molecule 1 (ICAM-1) levels and leucocyte integrin expression in polymicrobial sepsis. Mice were randomly assigned to a control group and an FO group. The control group was fed a medium-fat diet containing soyabean oil, whereas in the FO group, 70 % of the soyabean oil was replaced by FO for 3 weeks. After that, sepsis was induced by caecal ligation and puncture (CLP) in the experimental groups and mice were killed at 0, 6, 12 and 24 h, respectively, after CLP. Results showed that compared with the control group, plasma ICAM-1 levels were higher in the FO group 6 h after CLP. Intra-lymphocyte interferon-γ expression in the FO group was lower, whereas IL-4 expression was higher than in the control group 12 and 24 h after CLP. The expression of leucocyte integrin was significantly higher in the FO group 12 and 24 h after CLP. The FO group had higher IL-6 levels at 12 h in the lungs, at 6 and 12 h in the kidneys, and at 6, 12 and 24 h in the intestines after CLP. The survival rate did not differ between the two groups after CLP. The present findings suggest that pretreatment with an FO diet enhances adhesion molecule and inflammatory cytokine expressions during sepsis, which might aggravate the inflammatory reaction and increase neutrophil infiltration into tissues. In addition, FO diet promotes the Th2-type response and suppresses cellular immune response in polymicrobial sepsis.

The role of intercellular adhesion molecule 1 and neutrophils in acute pancreatitis and pancreatitis-associated lung injury

1999 ◽  
Vol 116 (3) ◽  
pp. 694-701 ◽  
Author(s):  
Jean-Louis Frossard ◽  
Ashok Saluja ◽  
Lakshmi Bhagat ◽  
Hong Sik Lee ◽  
Madhav Bhatia ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Lung Injury ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

scholarly journals Asef mediates HGF protective effects against LPS-induced lung injury and endothelial barrier dysfunction

2015 ◽  
Vol 308 (5) ◽  
pp. L452-L463 ◽  
Author(s):  
Fanyong Meng ◽  
Angelo Meliton ◽  
Nurgul Moldobaeva ◽  
Gokhan Mutlu ◽  
Yoshihiro Kawasaki ◽  
...  
Keyword(s):  
Lung Injury ◽  
Adhesion Molecule ◽  
Endothelial Barrier ◽  
Intercellular Adhesion Molecule ◽  
Protective Effects ◽  
Nucleotide Exchange ◽  
Intercellular Adhesion Molecule 1 ◽  
Barrier Dysfunction ◽  
Gram Negative ◽  
Anti Inflammatory

Increased vascular endothelial permeability and inflammation are major pathological mechanisms of pulmonary edema and its life-threatening complication, the acute respiratory distress syndrome (ARDS). We have previously described potent protective effects of hepatocyte growth factor (HGF) against thrombin-induced hyperpermeability and identified the Rac pathway as a key mechanism of HGF-mediated endothelial barrier protection. However, anti-inflammatory effects of HGF are less understood. This study examined effects of HGF on the pulmonary endothelial cell (EC) inflammatory activation and barrier dysfunction caused by the gram-negative bacterial pathogen lipopolysaccharide (LPS). We tested involvement of the novel Rac-specific guanine nucleotide exchange factor Asef in the HGF anti-inflammatory effects. HGF protected the pulmonary EC monolayer against LPS-induced hyperpermeability, disruption of monolayer integrity, activation of NF-kB signaling, expression of adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and production of IL-8. These effects were critically dependent on Asef. Small-interfering RNA-induced downregulation of Asef attenuated HGF protective effects against LPS-induced EC barrier failure. Protective effects of HGF against LPS-induced lung inflammation and vascular leak were also diminished in Asef knockout mice. Taken together, these results demonstrate potent anti-inflammatory effects by HGF and delineate a key role of Asef in the mediation of the HGF barrier protective and anti-inflammatory effects. Modulation of Asef activity may have important implications in therapeutic strategies aimed at the treatment of sepsis and acute lung injury/ARDS-induced gram-negative bacterial pathogens.

Sign in / Sign up

Export Citation Format

Share Document