Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall

Blank, Fabian; Wehrli, Marc; Lehmann, Andrea; Baum, Oliver; Gehr, Peter; Garnier, Christophe von; Rothen‐Rutishauser, Barbara

doi:10.1016/j.imbio.2010.02.006

Cited by 78 publications

(68 citation statements)

References 43 publications

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“…4B). Even though macrophages may transfer spores or antigenic material to CX3CR1-DCs, as suggested by previous in vitro work (25), we could neither observe such a transfer nor rule out that possibility, as infected macrophages appeared to be in close contact with DCs ( Fig. 5A; see also Video S9 in the supplemental material) and with infected CX3CR1 cells (Fig.…”

Section: Resultsmentioning

confidence: 57%

“…5B). This mechanism was recently suggested in vitro (25) but, to our knowledge, has never been reported in situ or in vivo. Nevertheless, directed cytokine release or ligand-receptor triggering during long-duration (Ͼ30-min) contact between macrophage and DC is most likely and may impact the delicate balance between tolerance and immunity within the lung.…”

Section: Discussionmentioning

confidence: 69%

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Two-Photon Intravital Imaging of Lungs during Anthrax Infection Reveals Long-Lasting Macrophage-Dendritic Cell Contacts

et al. 2014

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eThe dynamics of the lung immune system at the microscopic level are largely unknown because of inefficient methods of restraining chest motion during image acquisition. In this study, we developed an improved intravital method for two-photon lung imaging uniquely based on a posteriori parenchymal tissue motion correction. We took advantage of the alveolar collagen pattern given by the second harmonic generation signal as a reference for frame registration. We describe here for the first time a detailed dynamic account of two major lung immune cell populations, alveolar macrophages and CD11b-positive dendritic cells, during homeostasis and infection by spores of Bacillus anthracis, the agent of anthrax. We show that after alveolar macrophages capture spores, CD11b-positive dendritic cells come in prolonged contact with infected macrophages. Dendritic cells are known to carry spores to the draining lymph nodes and elicit the immune response in pulmonary anthrax. The intimate and long-lasting contacts between these two lines of defense may therefore coordinate immune responses in the lung through an immunological synapse-like process.T he lung is a crucial and yet very delicate organ dedicated to gas exchange through a thin alveolar-capillary wall (1). The obscure side of this highly efficient system is the constitutive fragility of its extensive exchange surfaces. The tour de force of the lungassociated immune system consists of its innate ability to protect against infection and pollutants while maintaining an anti-inflammatory environment (2). This complicated balance is achieved by a network of scattered cells such as alveolar macrophages on the outer side of the alveoli and different subsets of interstitial dendritic cells (DCs) (3).Recent advances in intravital microscopy (IVM) using twophoton excitation fluorescence (TPEF) have profoundly improved our understanding of the immune system dynamics in most organs, except the lungs (4). A detailed account of hostpathogen interactions in diverse tissues has been given (5-11), but lung immune system investigation by IVM has lagged due to the lack of a noninvasive and effective method taking into account lung features.Recent studies have addressed rigorous lung parenchyma IVM using TPEF in inflammation models (12). Two alternative a priori stabilization methods have been used by others to restrain movement compatible with imaging, based either on gluing the parenchyma onto a frame (13) or on a suction system stabilizing the lung under a glass window (14). These techniques, although effective for various purposes, are not optimal, as they alter the physiological motion of the parenchyma and may provoke unexpected reactions.We describe here an alternative approach for studying the lung by IVM based uniquely on a posteriori tissue motion correction. We take advantage of the fibrillar collagen pattern given by second harmonic generation (SHG) signals as a reference for frame registration and removal of wobbling images. This method allows acquisition in two spatial dime...

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Section: Resultsmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 69%

Two-Photon Intravital Imaging of Lungs during Anthrax Infection Reveals Long-Lasting Macrophage-Dendritic Cell Contacts

et al. 2014

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“…Using membrane filter supports, a triple cell culture model of the bronchial epithelium has been developed with airway epithelial cells cultured on the upper surface of the filter support until confluent, followed by introduction of macrophages onto the apical surface and dendritic cells basolaterally Rothen-Rutishauser et al, 2005). In this model, macrophages and dendritic cells were able to make contact with each other without breaking down the epithelial barrier by expression of tight junction proteins; an exchange of particulates between macrophages and dendritic cells was also possible (Blank et al, 2011). Another triple cell culture model is described by Farcal et al (2013).…”

Section: In Silico Modelingmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

124

103

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SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

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“…As we are not able to differentiate between both immune cell types by direct antibody staining due to embedding in the collagen layer, it is not possible to state which immune cell does the majority of nanoparticle or liposome processing. However, previous studies in a triple culture model of the alveolar mucosa found a preferential uptake by monocyte-derived macrophages, which then passed on the particulate cargo to the dendritic cells for further antigen processing and induction of an immune answer (Blank et al, 2011).…”

Section: Discussionmentioning

confidence: 90%

Screening of budesonide nanoformulations for treatment of inflammatory bowel disease in an inflamed 3D cell-culture model

Leonard

Ali²,

Collnot

et al. 2012

ALTEX

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Summary Drug formulation screenings for treatment of inflammatory bowel disease (IBD) are mostly conducted in chemically induced rodent models that represent acute injury-caused inflammation instead of a chronic condition. To accurately screen drug formulations for chronic IBD, a relevant model that mimics the chronic condition in vitro is urgently needed. In an effort to reduce and potentially replace this scientifically and ethically questionable animal testing for IBD drugs, our laboratory has developed an in vitro model for the inflamed intestinal mucosa observed in chronic IBD, which allows high-throughput screening of anti-inflammatory drugs and their formulations. The in vitro model consists of intestinal epithelial cells, human blood-derived macrophages, and dendritic cells that are stimulated by the inflammatory cytokine interleukin-1β. In this study, the model was utilized for evaluation of the efficacy and deposition of budesonide, an anti-inflammatory drug, in three different pharmaceutical formulations: (1) a free drug solution, (2) encapsulated into PLGA nanoparticles, and (3) encapsulated into liposomes. The in vitro model of the inflamed intestinal mucosa demonstrated its ability to differentiate therapeutic efficacy among the formulations while maintaining the convenience of conventional in vitro studies and adequately representing the complex pathophysiological changes observed in vivo.

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Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall

Cited by 78 publications

References 43 publications

Two-Photon Intravital Imaging of Lungs during Anthrax Infection Reveals Long-Lasting Macrophage-Dendritic Cell Contacts

Two-Photon Intravital Imaging of Lungs during Anthrax Infection Reveals Long-Lasting Macrophage-Dendritic Cell Contacts

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Screening of budesonide nanoformulations for treatment of inflammatory bowel disease in an inflamed 3D cell-culture model

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