scholarly journals Targeted Ablation of AIMP1 in Lipopolysaccharide-induced Acute Lung Injury

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Chris O’Connor ◽  
Margaret Schwarz, MD ◽  
Daniel Lee, PhD
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Club Cell ◽  
Significant Difference ◽  
Club Cells ◽  
Emap Ii ◽  
Intratracheal Delivery

Background and Hypothesis: Infants with Bronchopulmonary dysplasia (BPD), a chronic lung disease of premature infants, are more susceptible to acute lung injury (ALI). Endothelial-Monocyte Activating Polypeptide II (EMAP II, encoded by Aimp1) is a proinflammatory cytokine that originates from bronchiolar club cells and plays a role in the inflammatory response during BPD development. Prolonged EMAP II exposure has been shown to worsen BPD pathogenesis by activating alveolar macrophages. The targeted ablation of EMAP II in the bronchial club cells of a mouse model (Scgb1a1-ERTCre;Aimp1/fl/fl) is hypothesized to decrease the inflammatory effects of ALI. Experimental Design: Aged-matched littermate mice (ages ranging from 20-25 weeks) with Tamoxifen inducible, Cremediated, bronchial club cell specific ablation of Aimp1 (Scgb1a1-ERTCre;Aimp1/fl/fl, denoted cKO) or with only partial ablation (Scgb1a1-ERT2Cre;Aimp1/fl/wt denoted Ctrl) were given three doses of 120 micro-liters of 20mg/ml tamoxifen over a seven day period. 24 hours after the final dose they were administered a single intratracheal delivery of lipopolysaccharide (LPS) (5mg/kg) 24 hours later immunohistochemistry (IHC) for EMAP II and inflammation was assessed by immunoblotting (IB) for IL-6 in bronchoalveolar lavage (BAL) and cytospin of BAL. Results: IHC showed a decrease of EMAP II expression in the bronchioles of the cKO as compared to ctrl. IL-6 was increased 1.95 fold in the BAL fluid of cKO by IB. Cytospin analysis showed: (Cell Type: Ctrl%, cKo%), Macrophages: 4.66%, 4.70%, Mature neutrophils: 44.44%, 60.25%, Banded Neutrophils: 41.93%, 26.20%, Lymphocytes: 4.30%, 5.10%, Eosinophils: 2.51%, 2.10%, Monocytes: 2.15%, 1.64%. Conclusions: Ablation of bronchial club cell EMAP II, in LPS-induced ALI increased the amount of IL-6 and percentage of mature neutrophils in bronchoalveolar lavage fluid. No significant difference in macrophage were noted in either group. These findings suggest that EMAP II influences immune response time; however, more experiments would be required to establish a link.

A rise of MMP-2 and MMP-9 in bronchoalveolar lavage fluid is associated with acute lung injury after cardiopulmonary bypass in a swine model

Perfusion ◽  
2003 ◽  
Vol 18 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Wolfgang Eichler ◽  
J F Matthias Bechtel ◽  
Jan Schumacher ◽  
Johanna A Wermelt ◽  
Karl-Friedrich Klotz ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Cardiopulmonary Bypass ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Swine Model ◽  
Tissue Samples ◽  
Pulmonary Capillary ◽  
A Prospective Study

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.

Dynamic mechanical consequences of deep inflation in mice depend on type and degree of lung injury

2004 ◽  
Vol 96 (1) ◽  
pp. 293-300 ◽  
Author(s):  
Gilman Allen ◽  
Jason H. T. Bates
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Fluid Pressure ◽  
Lavage Fluid ◽  
Forced Oscillations ◽  
Positive End Expiratory Pressure ◽  
Reduced Pressure ◽  
Volume Curve

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.

Increased claudin-3, -4 and -18 levels in bronchoalveolar lavage fluid reflect severity of acute lung injury

Respirology ◽  
2013 ◽  
Vol 18 (4) ◽  
pp. 643-651 ◽  
Author(s):  
Wenting Jin ◽  
Linyi Rong ◽  
Yinkun Liu ◽  
Yuanlin Song ◽  
Yan Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid

scholarly journals Hypothermia Induced by Adenosine5′-Monophosphate Attenuates Acute Lung Injury Induced by LPS in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Zhimin Miao ◽  
Shulai Lu ◽  
Na Du ◽  
Weiting Guo ◽  
Jidong Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Inflammatory Cytokine ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Acute Injury ◽  
Pathological Changes ◽  
Inflammatory Reactions ◽  
Cytokine Levels

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.

The Fate of Antioxidant Enzymes in Bronchoalveolar Lavage Fluid Over 7 Days in Mice with Acute Lung Injury

2003 ◽  
Vol 15 (7) ◽  
pp. 675-685 ◽  
Author(s):  
Alfred M. Sciuto ◽  
Matthew B. Cascio ◽  
Theodore S. Moran ◽  
Jeffry S. Forster
Keyword(s):  
Antioxidant Enzymes ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid

scholarly journals IL-6 knockout alleviates inflammatory response and improve acute lung injury via regulating macrophage polarization in sepsis

2021 ◽  
Author(s):  
Jinxin Zhang ◽  
Kuo Shen ◽  
Jiangang Xie ◽  
Shanshou Liu ◽  
Xiaozhi Bai ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Western Blot ◽  
Bronchoalveolar Lavage ◽  
Inflammatory Cytokines ◽  
Lung Tissue ◽  
General Condition ◽  
Death Rate ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid

Abstract BackgroundSepsis is a fatal disease with a high rate of morbidity and mortality, during which acute lung injury is the earliest and most serious complication. Macrophage plays a crucial role in the initiation and progress of sepsis. This study meant to explore the effect of IL-6 knockout in CLP induced sepsis.MethodsIn this study, cecal ligation and puncture (CLP) was performed on wildtype and interleukin 6 (IL-6) knockout C57 mice. General condition and death rate of sepsis mice were observed. organ samples (lungs, livers, kidneys and hearts) and serum were collected for histology observation and inflammatory cytokine detection. Lung tissue injury detection were conducted via lung injury score, wet/dry ration and protein concentrations measurement of Bronchoalveolar lavage fluid (BALF). In in vivo studies, RAW264.7 macrophages were transfected with IL-6 specific siRNA and treated with LPS. After exposed to IL-6 specific siRNA and LPS, expression of inflammatory cytokines interleukin 1 (IL-1), tumor necrosis factor- (TNF-), IL-6 and interleukin 10 (IL-10) were detected by RT-qPCR, concentration of IL-1 and TNF- in culture supernatant were detected by ELISA and M1 and M2 markers were detected by western blot and flow cytometry.ResultsWe constructed CLP induced sepsis models and found that inhibition of IL-6 could improve general condition and death rate of sepsis mice. Mice in IL-6 knockout group display improved tissue damage, especially in the lung tissue. IL-6 knockout relieved inflammatory cytokines storm in both serum and bronchoalveolar lavage fluid while polarized macrophage to an anti-inflammatory M2 phenotype. In cell model, inhibition of IL-6 could alleviate LPS induced expression of inflammatory cytokines IL-1, TNF-, and IL-6 in macrophages. Western blot and Flow cytometry results indicated that expression of M1 markers (iNOS and CD86) in LPS stimulated macrophages were significantly declined while M2 (Arg-1 and CD206) were enhanced when expression of IL-6 was blocked.Conclusion Inhibition of IL-6 alleviated LPS induced inflammation and exerted protective effect in sepsis via regulating macrophage function and polarization.

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