scholarly journals Prophylactic Inhalation of L-Alanyl-L-Glutamine Enhances Heat Shock Protein 72 and Attenuates Endotoxin-Induced Lung Injury in Rats

2015 ◽  
pp. 505-512 ◽  
Author(s):  
I.-C. CHUANG ◽  
M.-S. HUANG ◽  
L.-J. HUANG ◽  
S.-H. CHOU ◽  
T.-N. TSAI ◽  
...  

Studies have demonstrated that heat shock protein 70 (HSP70) plays an important role in the protection of stressed organisms. The development of strategies for enhancing HSPs expression may provide novel means of minimizing inflammatory lung conditions, such as acute lung injury. This study aimed to examine the effect of L-alanyl-L-glutamine (GLN) inhalation in enhancing pulmonary HSP72 (inducible HSP70) expression and attenuating lung damage in a model of acute lung injury induced by Lipopolysaccharide (LPS) inhalation. The experimental rats were randomly assigned to one of four experimental groups: (1) NS: saline inhalation; (2) NS-LPS: pretreatment by saline inhalation 12 h before LPS inhalation; (3) GLN: glutamine inhalation; (4) GLN-LPS: pretreatment by glutamine inhalation 12 h before LPS inhalation. The results show that GLN compared with saline administration, led to significant increase in lung HSP72 both in non LPS-treated rats and LPS-treated rats. In LPS-treated rats, pretreatment by GLN inhalation produced less lung injury as evidenced by the decrease in lung injury score and dramatic decrease in lactate dehydrogenase (LDH) activity and polymorphonuclear leukocyte cell differentiation counts (PMN %) in the bronchoalveolar lavage fluid. The study indicates that prophylactic glutamine inhalation associated with the enhancement of HSP72 synthesis attenuates tissue damage in experimental lung injury.

2021 ◽  
Author(s):  
Irina N. Baranova ◽  
Alexander V. Bocharov ◽  
Tatyana G. Vishnyakova ◽  
Zhigang Chen ◽  
Anna A. Birukova ◽  
...  

Recent studies suggest an anti-inflammatory protective role for class B scavenger receptor BI (SR-BI) in endotoxin-induced inflammation and sepsis. Other data, including ours, provide evidence for an alternative role of SR-BI, facilitating bacterial and endotoxin uptake, and contributing to inflammation and bacterial infection. Enhanced endotoxin susceptibility of SR-BI deficient mice due to their anti-inflammatory glucocorticoid deficiency complicates understanding SR-BI’s role in endotoxemia/sepsis, calling for use of alternative models. In this study, using hSR-BI and hSR-BII transgenic mice, we found that SR-BI and to a lesser extent its splicing variant SR-BII, protects against LPS-induced lung damage. At 20 hours after intratracheal LPS instillation the extent of pulmonary inflammation and vascular leakage was significantly lower in hSR-BI and hSR-BII transgenic mice compared to wild type mice. Higher bronchoalveolar lavage fluid (BALF) inflammatory cell count and protein content as well as lung tissue neutrophil infiltration found in wild type mice was associated with markedly (2-3 times) increased pro-inflammatory cytokine production as compared to transgenic mice following LPS administration. Markedly lower endotoxin levels detected in BALF of transgenic vs. wild type mice along with the significantly increased BODIPY-LPS uptake observed in lungs of hSR-BI and hSR-BII mice 20 hours after the IT LPS injection suggest that hSR-BI and hSR-BII-mediated enhanced LPS clearance in the airways could represent the mechanism of their protective role against LPS-induced acute lung injury.


Perfusion ◽  
2003 ◽  
Vol 18 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Wolfgang Eichler ◽  
J F Matthias Bechtel ◽  
Jan Schumacher ◽  
Johanna A Wermelt ◽  
Karl-Friedrich Klotz ◽  
...  

Postoperative acute lung injury (ALI) contributes to the morbidity and mortality following cardiopulmonary bypass (CPB). To determine whether the presence of matrix metalloproteinases (MMPs) is associated with ALI after CPB, MMP-2 and MMP-9 activities in bronchoalveolar lavage fluid (BALF) were compared with parameters indicating impaired gas exchange. In a prospective study, 17 minipigs were subjected to CPB for 60 min. Before and at five and 180 min after CPB, MMP-2 and MMP-9 were assayed in BALF and the arterial-alveolar gradient of oxygen tension (AaDO2), the pulmonary capillary wedge pressure (PCWP) and the water content of lung tissue samples (Wt) were evaluated and compared with baseline values. MMP-2 and MMP-9 increased significantly 5 minutes (2.1- and 6.2-fold, respectively) and 180 minutes (3.4- and 14.3-fold, respectively) post-CPB. AaDO2 and Wt, but not PCWP, increased significantly 180 minutes after CPB and only AaDO2, but not PCWP or Wt, was significantly correlated with MMP-2 (r/0.66, p/0.006) and MMP-9 (r/0.62, p/0.01). In conclusion, high levels of MMP-2 and MMP-9 in the pulmonary compartment are associated with ALI after CPB.


2004 ◽  
Vol 96 (1) ◽  
pp. 293-300 ◽  
Author(s):  
Gilman Allen ◽  
Jason H. T. Bates

In a previous study (Allen G, Lundblad LK, Parsons P, and Bates JH. J Appl Physiol 93: 1709-1715 , 2002), our laboratory used deep inflations (DI) in mice to show that recruitment of closed lung units can be a very transient phenomenon in lung injury. The purpose of this study was to investigate how this transience of lung recruitment depends on the nature and degree of acute lung injury. Mice were administered 50 μl of either saline ( n = 8), 0.01 M ( n = 9) or 0.025 M ( n = 8) hydrochloric acid, or 50 μg ( n = 10) or 150 μg ( n = 6) of LPS and were mechanically ventilated 24-48 h later. At various levels of positive end-expiratory pressure, two DIs were delivered, and forced oscillations were used to obtain a measure of lung stiffness ( H) periodically over 7 min. After LPS exposure, pressure-volume curve hysteresis and recovery in H after DI were no different from saline-exposed controls despite 500 times more neutrophils in bronchoalveolar lavage fluid. Pressure-volume hysteresis and recovery in H were increased in acid-exposed mice ( P < 0.001) and were correlated with bronchoalveolar lavage fluid protein content ( R = 0.81). Positive end-expiratory pressure reduced recovery in H in all groups ( P < 0.01) but reduced pressure-volume hysteresis in the acid-injured groups only ( P < 0.001). We conclude that the effects of DIs in acute lung injury depend on the degree of lung injury but only to the extent that this injury reflects a disruption of the air-liquid interface.


Respirology ◽  
2013 ◽  
Vol 18 (4) ◽  
pp. 643-651 ◽  
Author(s):  
Wenting Jin ◽  
Linyi Rong ◽  
Yinkun Liu ◽  
Yuanlin Song ◽  
Yan Li ◽  
...  

2014 ◽  
Vol 155 (1) ◽  
pp. 60-70 ◽  
Author(s):  
Lisa Harlow ◽  
Bernadette R. Gochuico ◽  
Ivan O. Rosas ◽  
Tracy J. Doyle ◽  
Juan C. Osorio ◽  
...  

2011 ◽  
Vol 121 (5) ◽  
pp. 223-231 ◽  
Author(s):  
Hung-Jung Lin ◽  
Chia-Ti Wang ◽  
Ko-Chi Niu ◽  
Chungjin Gao ◽  
Zhuo Li ◽  
...  

HHP (hypobaric hypoxia preconditioning) induces the overexpression of HSP70 (heat-shock protein 70), as well as tolerance to cerebral ischaemia. In the present study, we hypothesized that HHP would protect against HAE (high-altitude exposure)-induced acute lung injury and oedema via promoting the expression of HSP70 in lungs prior to the onset of HAE. At 2 weeks after the start of HHP, animals were exposed to a simulated HAE of 6000 m in a hypobaric chamber for 24 h. Immediately after being returned to ambient pressure, the non-HHP animals had higher scores of alveolar oedema, neutrophil infiltration and haemorrhage, acute pleurisy (e.g. increased exudate volume, increased numbers of polymorphonuclear cells and increased lung myeloperoxidase activity), increased pro-inflammatory cytokines [e.g. TNF-α (tumour necrosis factor-α), IL (interleukin)-1β and IL-6], and increased cellular ischaemia (i.e. glutamate and lactate/pyruvate ratio) and oxidative damage [glycerol, NOx (combined nitrate+nitrite) and 2,3-dihydroxybenzoic acid] markers in the BALF (bronchoalveolar fluid). HHP, in addition to inducing overexpression of HSP70 in the lungs, significantly attenuated HAE-induced pulmonary oedema, inflammation, and ischaemic and oxidative damage in the lungs. The beneficial effects of HHP in preventing the occurrence of HAE-induced pulmonary oedema, inflammation, and ischaemic and oxidative damage was reduced significantly by pretreatment with a neutralizing anti-HSP70 antibody. In conclusion, HHP may attenuate the occurrence of pulmonary oedema, inflammation, and ischaemic and oxidative damage caused by HAE in part via up-regulating HSP70 in the lungs.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Zhimin Miao ◽  
Shulai Lu ◽  
Na Du ◽  
Weiting Guo ◽  
Jidong Zhang ◽  
...  

We have built a rat’s model to investigate whether the hypothermia induced by adenosine 5′-monophosphate (5′-AMP) (AIH) could attenuate acute lung injury induced by LPS in rats. We detected the inflammatory cytokine levels in the plasma and bronchoalveolar lavage fluid samples, and we analyzed the pathological changes in the lungs. We have found that AIH can effectively inhibit acute inflammatory reactions and protect the lung from acute injury induced by LPS in rats.


2003 ◽  
Vol 15 (7) ◽  
pp. 675-685 ◽  
Author(s):  
Alfred M. Sciuto ◽  
Matthew B. Cascio ◽  
Theodore S. Moran ◽  
Jeffry S. Forster

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