The Experts below are selected from a list of 13179 Experts worldwide ranked by ideXlab platform
Sina A Gharib - One of the best experts on this subject based on the ideXlab platform.
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Alveolar Macrophage transcriptional programs are associated with outcomes in acute respiratory distress syndrome
American Journal of Respiratory and Critical Care Medicine, 2019Co-Authors: Eric D Morrell, Pavan K Bhatraju, Carmen Mikacenic, Frank Radella, Anne M Manicone, Renee D Stapleton, Mark M Wurfel, Sina A GharibAbstract:Rationale: Serial measurements of Alveolar Macrophage (AM) transcriptional changes in patients with acute respiratory distress syndrome (ARDS) could identify cell-specific biological programs that ...
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cytometry tof identifies Alveolar Macrophage subtypes in acute respiratory distress syndrome
JCI insight, 2018Co-Authors: Eric D Morrell, Mark M Wurfel, Sina A Gharib, Alice E Wiedeman, Alice S Long, Eoin T West, Shawn J Skerrett, Carmen MikacenicAbstract:Studies in human peripheral blood monocyte-derived Macrophages in vitro have shown clear evidence that multiple Macrophage polarization states exist. The extent to which different Alveolar Macrophage (AM) polarization states exist in homeostasis or in the setting of severe injury such as acute respiratory distress syndrome (ARDS) is largely unknown. We applied single-cell cytometry TOF (CyTOF) to simultaneously measure 36 cell-surface markers on CD45+ cells present in bronchoAlveolar lavage from healthy volunteers, as well as mechanically ventilated subjects with and without ARDS. Visualization of the high-dimensional data with the t-distributed stochastic neighbor embedding algorithm demonstrated wide diversity of cell-surface marker profiles among CD33+CD71+CD163+ AMs. We then used a κ-nearest neighbor density estimation algorithm to statistically identify distinct Alveolar myeloid subtypes, and we discerned 3 AM subtypes defined by CD169 and PD-L1 surface expression. The percentage of AMs that were classified into one of the 3 AM subtypes was significantly different between healthy and mechanically ventilated subjects. In an independent cohort of subjects with ARDS, PD-L1 gene expression and PD-L1/PD-1 pathway-associated gene sets were significantly decreased in AMs from patients who experienced prolonged mechanical ventilation or death. Unsupervised CyTOF analysis of Alveolar leukocytes from human subjects has potential to identify expected and potentially novel myeloid populations that may be linked with clinical outcomes.
Wei Wang - One of the best experts on this subject based on the ideXlab platform.
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antiviral and anti inflammatory treatment with multifunctional Alveolar Macrophage like nanoparticles in a surrogate mouse model of covid 19
Advanced Science, 2021Co-Authors: Wei Wang, Weifeng Song, Zheng Zhao, Qingqin Tan, Zhaoyan Zhao, Lantian Tang, Tianchuan Zhu, Jialing Yin, Jun BaiAbstract:The pandemic of coronavirus disease 2019 (COVID-19) is continually worsening. Clinical treatment for COVID-19 remains primarily supportive with no specific medicines or regimens. Here, the development of multifunctional Alveolar Macrophage (AM)-like nanoparticles (NPs) with photothermal inactivation capability for COVID-19 treatment is reported. The NPs, made by wrapping polymeric cores with AM membranes, display the same surface receptors as AMs, including the coronavirus receptor and multiple cytokine receptors. By acting as AM decoys, the NPs block coronavirus from host cell entry and absorb various proinflammatory cytokines, thus achieving combined antiviral and anti-inflammatory treatment. To enhance the antiviral efficiency, an efficient photothermal material based on aggregation-induced emission luminogens is doped into the NPs for virus photothermal disruption under near-infrared (NIR) irradiation. In a surrogate mouse model of COVID-19 caused by murine coronavirus, treatment with multifunctional AM-like NPs with NIR irradiation decreases virus burden and cytokine levels, reduces lung damage and inflammation, and confers a significant survival advantage to the infected mice. Crucially, this therapeutic strategy may be clinically applied for the treatment of COVID-19 at early stage through atomization inhalation of the NPs followed by NIR irradiation of the respiratory tract, thus alleviating infection progression and reducing transmission risk.
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Antiviral and Anti‐Inflammatory Treatment with Multifunctional Alveolar Macrophage‐Like Nanoparticles in a Surrogate Mouse Model of COVID‐19
'Wiley', 2021Co-Authors: Wei Wang, Weifeng Song, Zheng Zhao, Qingqin Tan, Zhaoyan Zhao, Lantian Tang, Tianchuan Zhu, Jialing Yin, Jun BaiAbstract:Abstract The pandemic of coronavirus disease 2019 (COVID‐19) is continually worsening. Clinical treatment for COVID‐19 remains primarily supportive with no specific medicines or regimens. Here, the development of multifunctional Alveolar Macrophage (AM)‐like nanoparticles (NPs) with photothermal inactivation capability for COVID‐19 treatment is reported. The NPs, made by wrapping polymeric cores with AM membranes, display the same surface receptors as AMs, including the coronavirus receptor and multiple cytokine receptors. By acting as AM decoys, the NPs block coronavirus from host cell entry and absorb various proinflammatory cytokines, thus achieving combined antiviral and anti‐inflammatory treatment. To enhance the antiviral efficiency, an efficient photothermal material based on aggregation‐induced emission luminogens is doped into the NPs for virus photothermal disruption under near‐infrared (NIR) irradiation. In a surrogate mouse model of COVID‐19 caused by murine coronavirus, treatment with multifunctional AM‐like NPs with NIR irradiation decreases virus burden and cytokine levels, reduces lung damage and inflammation, and confers a significant survival advantage to the infected mice. Crucially, this therapeutic strategy may be clinically applied for the treatment of COVID‐19 at early stage through atomization inhalation of the NPs followed by NIR irradiation of the respiratory tract, thus alleviating infection progression and reducing transmission risk
Robert Landsiedel - One of the best experts on this subject based on the ideXlab platform.
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an in vitro Alveolar Macrophage assay for predicting the short term inhalation toxicity of nanomaterials
Journal of Nanobiotechnology, 2016Co-Authors: Martin Wiemann, Antje Vennemann, Ursula G Sauer, Karin Wiench, Lan Mahock, Robert LandsiedelAbstract:Background Most in vitro studies investigating nanomaterial pulmonary toxicity poorly correlate to in vivo inhalation studies. Alveolar Macrophages (AMs) play an outstanding role during inhalation exposure since they effectively clear the alveoli from particles. This study addresses the applicability of an in vitro Alveolar Macrophage assay to distinguish biologically active from passive nanomaterials.
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an in vitro Alveolar Macrophage assay for predicting the short term inhalation toxicity of nanomaterials
Journal of Nanobiotechnology, 2016Co-Authors: Martin Wiemann, Antje Vennemann, Ursula G Sauer, Karin Wiench, Lan Mahock, Robert LandsiedelAbstract:Most in vitro studies investigating nanomaterial pulmonary toxicity poorly correlate to in vivo inhalation studies. Alveolar Macrophages (AMs) play an outstanding role during inhalation exposure since they effectively clear the alveoli from particles. This study addresses the applicability of an in vitro Alveolar Macrophage assay to distinguish biologically active from passive nanomaterials. Rat NR8383 Alveolar Macrophages were exposed to 18 inorganic nanomaterials, covering AlOOH, BaSO4, CeO2, Fe2O3, TiO2, ZrO2, and ZnO NMs, amorphous SiO2 and graphite nanoplatelets, and two nanosized organic pigments. ZrO2 and amorphous SiO2 were tested without and with surface functionalization. Non-nanosized quartz DQ12 and corundum were used as positive and negative controls, respectively. The test materials were incubated with the cells in protein-free culture medium. Lactate dehydrogenase, glucuronidase, and tumour necrosis factor alpha were assessed after 16 h. In parallel, H2O2 was assessed after 1.5 h. Using the no-observed-adverse-effect concentrations (NOAECs) from available rat short-term inhalation studies (STIS), the test materials were categorized as active (NOAEC < 10 mg/m3) or passive. In vitro data reflected the STIS categorization if a particle surface area-based threshold of <6000 mm2/mL was used to determine the biological relevance of the lowest observed significant in vitro effects. Significant effects that were recorded above this threshold were assessed as resulting from test material-unspecific cellular ‘overload’. Test materials were assessed as active if ≥2 of the 4 in vitro parameters undercut this threshold. They were assessed as passive if 0 or 1 parameter was altered. An overall assay accuracy of 95 % was achieved. The in vitro NR8383 Alveolar Macrophage assay allows distinguishing active from passive nanomaterials. Thereby, it allows determining whether in vivo short-term inhalation testing is necessary for hazard assessment. Results may also be used to group nanomaterials by biological activity. Further work should aim at validating the assay.
David R Thickett - One of the best experts on this subject based on the ideXlab platform.
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acute respiratory distress syndrome is associated with impaired Alveolar Macrophage efferocytosis
European Respiratory Journal, 2021Co-Authors: Rahul Y Mahida, Aaron Scott, Dhruv Parekh, Sebastian T Lugg, Rowan Hardy, Gareth G Lavery, Michael A Matthay, Babu Naidu, Gavin D Perkins, David R ThickettAbstract:Acute respiratory distress syndrome (ARDS) is an inflammatory disorder of the lungs, with sepsis as the predominant aetiology. Despite advances in ventilation strategies, mortality for moderate to severe ARDS remains at 40-46% [1]. ARDS is associated with neutrophil influx into alveoli. Persistently high neutrophil and low Alveolar Macrophage (AM) numbers in broncho-Alveolar lavage (BAL) fluid are associated with greater mortality [2]. While the inflammatory Alveolar environment of early ARDS initially delays apoptosis, these neutrophils ultimately undergo apoptosis within alveoli [3]. Efficient efferocytosis of apoptotic neutrophils by AMs is critical for resolution of inflammation [3]. Apoptotic neutrophils may accumulate in ARDS due to defective AM efferocytosis and/or overwhelmed efferocytosis capacity, then undergo secondary necrosis, releasing inflammatory mediators into the Alveolar space [4]. This may contribute to the prolonged inflammation observed in ARDS. No study has previously assessed AM efferocytosis in ARDS, however monocyte-derived Macrophages (MDMs) from ARDS patients do have impaired efferocytosis [5]. We investigated whether ARDS patients have impaired AM efferocytosis and increased Alveolar neutrophil apoptosis. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Mahida has nothing to disclose. Conflict of interest: Dr. Scott has nothing to disclose. Conflict of interest: Dr. Parekh has nothing to disclose. Conflict of interest: Dr. Lugg has nothing to disclose. Conflict of interest: Dr. Hardy has nothing to disclose. Conflict of interest: Dr. Lavery has nothing to disclose. Conflict of interest: Dr. Matthay has nothing to disclose. Conflict of interest: Dr. Naidu has nothing to disclose. Conflict of interest: Dr. Perkins has nothing to disclose. Conflict of interest: Dr. Thickett has nothing to disclose.
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acute respiratory distress syndrome is associated with impaired Alveolar Macrophage efferocytosis
medRxiv, 2021Co-Authors: Rahul Y Mahida, Aaron Scott, Dhruv Parekh, Sebastian T Lugg, Rowan Hardy, Gareth G Lavery, Michael A Matthay, Babu Naidu, Gavin D Perkins, David R ThickettAbstract:ABSTRACT Background Alveolar Macrophage dysfunction may contribute to Acute Respiratory Distress Syndrome (ARDS) pathogenesis, however this has been little studied. Objective To investigate the pathophysiological link between Alveolar Macrophage efferocytosis, Alveolar neutrophil apoptosis and clinical outcomes in ARDS patients, and to determine whether efferocytosis can be restored. Methods Ventilated sepsis patients with or without ARDS underwent broncho-Alveolar lavage. Apoptosis of Alveolar neutrophils was assessed using flow cytometry. Alveolar Macrophages were isolated and used in flow cytometric efferocytosis assays with labelled apoptotic neutrophils. Alveolar Macrophages were also isolated from the lung tissue of lobectomy patients, then treated with pooled ARDS BAL fluid prior to functional assessment. Rac1 gene expression was assessed using RT-qPCR. Results Patients with sepsis-related ARDS have decreased Alveolar Macrophage efferocytosis and increased Alveolar neutrophil apoptosis compared to control ventilated sepsis patients. Across all ventilated sepsis patients, Alveolar Macrophage efferocytosis correlated negatively with Alveolar cytokines (IL-8, IL-1ra), duration of ventilation and mortality. ARDS BAL treatment of Alveolar Macrophages decreased efferocytosis and Rac1 gene expression, however bacterial phagocytosis was preserved. Unexpectedly, Alveolar Macrophage efferocytosis receptor expression (MerTK, CD206) decreased and expression of the anti-efferocytosis receptor SIRPα increased following ARDS BAL treatment. Rho-associated kinase inhibition partially restored Alveolar Macrophage efferocytosis in an in vitro model of ARDS. Conclusions Patients with sepsis-related ARDS have impaired Alveolar Macrophage efferocytosis, resulting in persistent inflammation from secondary neutrophil necrosis. This potentially has a negative effect on clinical outcomes, including mortality. Strategies to upregulate AM efferocytosis may be of value for attenuating inflammation in ARDS. Take home message ARDS patients have decreased Alveolar Macrophage efferocytosis, resulting in inflammation from secondary neutrophil necrosis, which contributes to worse clinical outcomes including mortality. Upregulation of efferocytosis may offer a therapeutic strategy.
Michael S Mulligan - One of the best experts on this subject based on the ideXlab platform.
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Alveolar Macrophage secretory products effect type 2 pneumocytes undergoing hypoxia reoxygenation
The Annals of Thoracic Surgery, 2008Co-Authors: Anton S Mccourtie, Alexander S Farivar, Steven M Woolley, Heather E Merry, Patrick S Wolf, Brendan Mackinnonpatterson, John Keech, Elizabeth Fitzsullivan, Michael S MulliganAbstract:Background Activation of the Alveolar Macrophage is centrally important to the development of lung ischemia reperfusion injury. Alveolar Macrophages and type 2 pneumocytes secrete a variety of proinflammatory mediators in response to oxidative stress. The manner in which they interact and how the Macrophage may influence pneumocyte responses in lung ischemia reperfusion injury is unknown. Utilizing an in vitro model of hypoxia and reoxygenation, we sought to determine if the proinflammatory response of type 2 pneumocytes to oxidative stress would be amplified by Alveolar Macrophage secretory products. Methods Cultured pneumocytes were exposed to control media or media from cultured Macrophages exposed to hypoxia and reoxygenation. Pneumocytes were subsequently subjected to hypoxia and reoxygenation and assessed for both nuclear translocation of nuclear factor kappa B and inflammatory cytokine and chemokine secretion. To examine for any reciprocal interactions, we reversed the experiment, exposing Macrophages to conditioned pneumocyte media. Results In the presence of media from stimulated Macrophages, production of proinflammatory mediators by type 2 pneumocytes was dramatically enhanced. In contrast, exposure of the Macrophage to conditioned pneumocyte media had an inhibitory effect on Macrophage responses subsequently exposed to hypoxia and reoxygenation. Conclusions The Alveolar Macrophage drives the development of lung reperfusion injury in part through amplification of the inflammatory response of type 2 pneumocytes subjected to hypoxia and reoxygenation.
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early activation of the Alveolar Macrophage is critical to the development of lung ischemia reperfusion injury
The Journal of Thoracic and Cardiovascular Surgery, 2003Co-Authors: Babu V Naidu, Alexander S Farivar, Steven M Woolley, Baiya Krishnadasan, Robert Thomas, Nico Van Rooijen, Edward D Verrier, Michael S MulliganAbstract:Abstract Objectives Activation of the Alveolar Macrophage is critical to the development of nonischemic inflammatory lung injury. The present studies were undertaken to determine whether the Alveolar Macrophage plays a similarly important role in lung ischemia-reperfusion injury. Methods The left lungs of male rats were rendered ischemic for 90 minutes and reperfused for up to 4 hours. Treated animals received liposome-encapsulated clodronate, which depletes Alveolar Macrophages. Injury was quantitated in terms of vascular permeability, tissue neutrophil accumulation, and bronchoAlveolar lavage fluid leukocyte, chemokine, and cytokine content. Lung homogenates were also analyzed for nuclear translocation of the transcription factors nuclear factor κB and activator of protein 1. Results Depletion of Alveolar Macrophages reduced lung vascular permeability by 53% compared with that seen in control animals (permeability indices: 0.88 ± 0.07 to 0.46 ± 0.04, P P Conclusion It is likely that the Alveolar Macrophage is the key early source of multiple proinflammatory mediators that orchestrate lung ischemia-reperfusion injury. Depleting Alveolar Macrophages is protective against injury, supporting its central role in oxidant stress–induced cytokine and chemokine release and the subsequent development of lung injury.