scholarly journals Intrabronchial application of extracellular histones shows no proinflammatory effects in swine in a translational pilot study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Robert Ruemmler ◽  
Alexander Ziebart ◽  
Elisabeth Britten ◽  
Moritz Gosling ◽  
Rene Rissel ◽  
...  
Keyword(s):  
Pilot Study ◽  
Porcine Model ◽  
Inflammatory Responses ◽  
Mortality Rates ◽  
Injury Model ◽  
Molecular Factor ◽  
Extracellular Histones ◽  
Lung Injury Model ◽  
In Vivo Effects

Abstract Objective Extracellular histones have been identified as one molecular factor that can cause and sustain alveolar damage and were linked to high mortality rates in critically ill patients. In this pilot study, we wanted to validate the proinflammatory in vivo effects of local histone application in a prospective translational porcine model. This was combined with the evaluation of an experimental acute lung injury model using intrabronchial lipopolysaccharides, which has been published previously. Results The targeted application of histones was successful in all animals. Animals showed decreased oxygenation after instillation, but no differences could be detected between the sham and histone treatments. The histologic analyses and inflammatory responses indicated that there were no differences in tissue damage between the groups.

scholarly journals Intrabronchial Application of Extracellular Histones Shows No Proinflammatory Effects in Swine in a Translational Pilot Study

2021 ◽  
Author(s):  
Robert Ruemmler ◽  
Alexander Ziebart ◽  
Elisabeth Britten ◽  
Moritz Gosling ◽  
Rene Rissel ◽  
...  
Keyword(s):  
Pilot Study ◽  
Porcine Model ◽  
Inflammatory Responses ◽  
Mortality Rates ◽  
Injury Model ◽  
Molecular Factor ◽  
Extracellular Histones ◽  
Lung Injury Model ◽  
In Vivo Effects

Abstract Objective: Extracellular histones have been identified as one molecular factor that can cause and sustain alveolar damage and were linked to high mortality rates in critically ill patients. In this pilot study, we wanted to validate the proinflammatory in vivo effects of local and systemic histone application in a prospective translational porcine model. This was combined with the evaluation of an experimental acute lung injury model using intrabronchial lipopolysaccharides, which has been published previously.Results: The targeted application of histones was successful in all animals. Animals showed decreased oxygenation after instillation, but no differences could be detected between the sham and histone treatments. Additionally, intravenous histone injection had no effect. The histologic analyses and inflammatory responses indicated that there were no differences in tissue damage between the groups.

scholarly journals In Vitro and In Vivo Effects of IGF-I on Adiposity in HIV-associated Metabolic Disease: A Pilot Study

2013 ◽  
Vol 44 (5) ◽  
pp. 361-369 ◽  
Author(s):  
Roy J. Kim ◽  
Sumit Vaghani ◽  
Larisa M. Zifchak ◽  
Joseph H. Quinn ◽  
Weimian He ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Pilot Study ◽  
Igf I ◽  
In Vivo Effects

scholarly journals Levonadifloxacin, a Novel Benzoquinolizine Fluoroquinolone, Modulates Lipopolysaccharide-Induced Inflammatory Responses in Human Whole-Blood Assay and Murine Acute Lung Injury Model

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Anasuya Patel ◽  
Ganesh V. Sangle ◽  
Jinal Trivedi ◽  
Sushant A. Shengule ◽  
Deepak Thorve ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Whole Blood ◽  
Inflammatory Responses ◽  
Immunomodulatory Activity ◽  
Human Whole Blood ◽  
Injury Model ◽  
Cytokine Levels ◽  
Lung Injury Model ◽  
Clinical Benefits

ABSTRACT Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizine fluoroquinolone, levonadifloxacin, was evaluated in lipopolysaccharide-stimulated human whole-blood (HWB) and mouse acute lung injury (ALI) models. Levonadifloxacin significantly mitigated the inflammatory responses in an HWB assay through inhibition of proinflammatory cytokines and in the ALI model by lowering lung total white blood cell count, myeloperoxidase, and cytokine levels. The immunomodulatory effect of levonadifloxacin, along with promising antibacterial activity, is expected to provide clinical benefits in the treatment of infections.

scholarly journals The role of endothelial PI3Kγ activity in neutrophil trafficking

Blood ◽  
2005 ◽  
Vol 106 (1) ◽  
pp. 150-157 ◽  
Author(s):  
Kamal D. Puri ◽  
Teresa A. Doggett ◽  
Ching-Yu Huang ◽  
Jason Douangpanya ◽  
Joel S. Hayflick ◽  
...  
Keyword(s):  
Critical Role ◽  
Fold Increase ◽  
Necrosis Factor Alpha ◽  
Catalytic Subunits ◽  
Injury Model ◽  
Lung Injury Model ◽  
Factor Alpha ◽  
Phosphoinositide 3 Kinase

Phosphoinositide 3-kinase gamma (PI3Kγ) in neutrophils plays a critical role in the directed migration of these cells into inflamed tissues. In this study, we demonstrate the importance of the endothelial component of PI3Kγ activity relative to its leukocyte counterpart in supporting neutrophil interactions with the inflamed vessel wall. Despite the reconstitution of class-Ib PI3K function in neutrophils of p110γ–/– mice, we observed a 45% reduction in accumulation of these cells in an acute lung injury model. Mechanistically, this appears to result from a perturbation in selectin-mediated adhesion as manifested by a 70% reduction in wild-type (WT) neutrophil attachment to and 17-fold increase in rolling velocities on p110γ–/– microvessels in vivo in response to tumor necrosis factor alpha (TNFα). This alteration in adhesion was further augmented by a deficiency in p110δ, suggesting that the activity of both catalytic subunits is required for efficient capture of neutrophils by cytokine-stimulated endothelium. Interestingly, E-selectin–mediated adhesion in p110γ–/– mice was impaired by more than 95%, but no defect in nuclear factor kappa B (NF-κB)–induced gene expression was observed. These findings suggest a previously unrecognized partnership between class-I PI3Ks expressed in leukocytes and endothelium, the combination of which is required for the efficient trafficking of immunocompetent cells to sites of inflammation.

In vivo Effects of Mutant HERG K+Channel Inhibition by Disopyramide in Patients with a Short QT-1 Syndrome: A Pilot Study

2007 ◽  
Vol 18 (11) ◽  
pp. 1157-1160 ◽  
Author(s):  
RAINER SCHIMPF ◽  
CHRISTIAN VELTMANN ◽  
CARLA GIUSTETTO ◽  
FIORENZO GAITA ◽  
MARTIN BORGGREFE ◽  
...  
Keyword(s):  
Pilot Study ◽  
K Channel ◽  
Channel Inhibition ◽  
In Vivo Effects

THE EFFECTS OF HEMODILUTION ON ACUTE INFLAMMATORY RESPONSES IN A BLEOMYCIN-INDUCED LUNG INJURY MODEL

2009 ◽  
Vol 35 (10) ◽  
pp. 841-857 ◽  
Author(s):  
Soon Ho Cheong ◽  
Jeong Han Lee ◽  
Kun Moo Lee ◽  
Kwang Rae Cho ◽  
Young Il Yang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Inflammatory Responses ◽  
Injury Model ◽  
Lung Injury Model

scholarly journals Excipient Enhanced Growth Aerosol Surfactant Replacement Therapy in an In Vivo Rat Lung Injury Model

2020 ◽  
Vol 33 (6) ◽  
pp. 314-322
Author(s):  
Franck J. Kamga Gninzeko ◽  
Michael S. Valentine ◽  
Cindy K. Tho ◽  
Sahil R. Chindal ◽  
Susan Boc ◽  
...  
Keyword(s):  
Lung Injury ◽  
Replacement Therapy ◽  
Rat Lung ◽  
Surfactant Replacement ◽  
Injury Model ◽  
Surfactant Replacement Therapy ◽  
Lung Injury Model

scholarly journals Extracellular histones trigger disseminated intravascular coagulation by lytic cell death

2020 ◽  
Author(s):  
Congqing Wu ◽  
Yan Zhang ◽  
Lan Li ◽  
Ankit Pandeya ◽  
Guoying Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Tissue Factor ◽  
Inflammatory Responses ◽  
Inflammasome Activation ◽  
List Type ◽  
Coagulation Activation ◽  
Eukaryotic Chromatin ◽  
Extracellular Histones ◽  
Dependent Mechanism

AbstractHistones are cationic nuclear proteins that are essential for the structure and functions of eukaryotic chromatin. However, extracellular histones trigger inflammatory responses and contribute to death in sepsis by unknown mechanisms. We recently reported that inflammasome activation and pyroptosis trigger coagulation activation through a tissue factor (TF)-dependent mechanism. Here, we show that histones trigger coagulation activation in vivo as evidenced by coagulation parameters and fibrin deposition in tissues. However, histone-induced coagulopathy was neither dependent on caspase 1/11 and gasdermin D (GSDMD), nor on TLR2 and TLR4, as deficiency of these genes in mice did not protect against histone-induced coagulopathy. Incubation of histones with macrophages induced lytic cell death and phosphatidylserine (PS) exposure, which is required for TF activity, a key initiator of coagulation. Neutralization of TF diminished histone-induced coagulation. Our findings reveal lytic cell death as a novel mechanism of histone-induce coagulation activation and thrombosis.Key PointsHistones trigger DIC in a tissue factor dependent mechanismHistones induce tissue factor activation through lytic cell death

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