Experimental lung research
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Acute lung injury (ALI) is often associated with sepsis and is the most common cause of acute respiratory failure. The authors evaluated the role of the heme oxygenase (HO)/carbon monoxide (CO) system on lung injury in a cecal ligation and puncture (CLP)-induced mouse model of ALI. The authors established CLP-induced ALI in C57BL/6 mice. ⋯ Hemin pretreatment also caused a significant decrease in plasma TM along with increased cell surface TM expression in lung tissue, suggesting attenuation of lung injury. Survival data showed that no difference for survival between CLP animals pretreated with hemin or Znpp. Taken together, HO-1 exerts its protective effects on CLP-induced ALI via regulating cell surface TM and APC expression and modulating blood coagulation.
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Pulmonary inflammation is the key pathological presentation of mechanical ventilation-induced lung injury (VILI), and synthetic RGDS peptide has been suggested to attenuate pulmonary inflammation. The present study aimed to determine whether RGDS peptide has protective effects on VILI. Rats received 4 hours of high tidal volume mechanical ventilation with or without pretreatment with RGDS. ⋯ At the end of 4 hours, rats that received 4 hours of mechanical ventilation exhibited serious pulmonary pathological changes, more polymorphonulear and mononuclear leukocyte recruitment, more tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) production, higher total protein contents in the bronchoalveolar lavage fluids (BALFs) and more lung phosphorylation of integrin β3 and nuclear factor-κB inhibitor (I-κB), and increased NF-κB p65 binding activity than did the control group. Administration of RGDS peptide tended to significantly inhibit all these changes induced by mechanical ventilation. These results suggested that RGDS pretreatment might improve VILI in rats by attenuating inflammatory cascade related to integrin αVβ3 and NF-κB.
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Idiopathic pulmonary fibrosis (IPF) is characterized by interstitial lung infiltrates, dyspnea, and progressive respiratory failure. Reports linking telomerase mutations to familial interstitial pneumonia (FIP) suggest that telomerase activity and telomere length maintenance are important in disease pathogenesis. To investigate the role of telomerase in lung fibrotic remodeling, intratracheal bleomycin was administered to mice deficient in telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) and to wild-type controls. ⋯ Telomere lengths were reduced in peripheral blood leukocytes and isolated type II AECs from F6 TERT-deficient and F4 TERC-deficient mice compared to controls. Telomerase deficiency in a murine model leads to telomere shortening, but does not predispose to enhanced bleomycin-induced lung fibrosis. Additional genetic or environmental factors may be necessary for development of fibrosis in the presence of telomerase deficiency.
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Chronic allograft rejection and bronchiolitis obliterans (BO) limited successful long-term outcome after lung transplantation (LTX). Reliable animal models are needed to study the pathogenesis of BO and to develop effective therapeutic strategies. The relevance of an available experimental LTX model without immunosuppression-the Fischer (F344)-Wistar Kyoto (WKY) rat strain combination-was analyzed. ⋯ At the same time, the allografts with BO-like lesions increased up to 100% in rats from CR. The F344-to-WKY rat LTX model allows detailed assessment of all features of acute and chronic pulmonary rejection representing a clinically relevant model. However, due to breeding differences resulting in various sublines of the same rat strain, the source and husbandary history of the animals is important for analysis of immuno-mediated processes.
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Excess production of neutrophil elastase contributes to the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the role of neutrophil elastase in the repair process following ALI/ARDS is not well understood. The objective of this study was to evaluate the effect of neutrophil elastase on the process of tissue repair after acute lung injury in mice. ⋯ Administration of the neutrophil elastase inhibitor also decreased the accumulation of neutrophils in the BALF, TGF-β1 activation, and expression of phospho-SMAD2/3. The authors conclude that inhibiting neutrophil elastase protects against the development of lung fibrosis after acute injury. In addition, these data suggest that this neutrophil elastase inhibitor has therapeutic potential for the fibroproliferative phase of ALI/ARDS.