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Frontiers in immunology. 2022 Jul 7. doi: 10.3389/fimmu.2022.895100. pmc: PMC9300899

A Barrier to Defend - Models of Pulmonary Barrier to Study Acute Inflammatory Diseases.

Herminghaus A¹, Kozlov AV², Szabó A³, Hantos Z⁴, Gylstorff S⁵, Kuebart A⁶, Aghapour M⁷, Wissuwa B⁸, Walles T⁹, Walles H¹⁰, Coldewey SM¹¹, Relja B¹²

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¹Department of Anaesthesiology, University of Duesseldorf, Duesseldorf, Germany.
²L Boltzmann Institute for Traumatology in Cooperation with AUVA and Austrian Cluster for Tissue Regeneration, Vienna, Austria.
³Institute of Surgical Research, University of Szeged, Szeged, Hungary.
⁴Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary.
⁵Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg, Germany.
⁶Department of Anaesthesiology, University of Duesseldorf, Duesseldorf, Germany.
⁷Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg, Germany.
⁸Department of Anaesthesiology and Intensive Care Medicine, Septomics Research Centre, Centre for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
⁹Department of Thoracic Surgery, Magdeburg University Medicine, Magdeburg, Germany.
¹⁰Research Campus STIMULATE, Otto-von-Guericke University, Magdeburg, Germany.
¹¹Department of Anaesthesiology and Intensive Care Medicine, Septomics Research Centre, Centre for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
¹²Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg, Germany.

Abstract

Pulmonary diseases represent four out of ten most common causes for worldwide mortality. Thus, pulmonary infections with subsequent inflammatory responses represent a major public health concern. The pulmonary barrier is a vulnerable entry site for several stress factors, including pathogens such as viruses, and bacteria, but also environmental factors e.g. toxins, air pollutants, as well as allergens. These pathogens or pathogen-associated molecular pattern and inflammatory agents e.g. damage-associated molecular pattern cause significant disturbances in the pulmonary barrier. The physiological and biological functions, as well as the architecture and homeostatic maintenance of the pulmonary barrier are highly complex. The airway epithelium, denoting the first pulmonary barrier, encompasses cells releasing a plethora of chemokines and cytokines, and is further covered with a mucus layer containing antimicrobial peptides, which are responsible for the pathogen clearance. Submucosal antigen-presenting cells and neutrophilic granulocytes are also involved in the defense mechanisms and counterregulation of pulmonary infections, and thus may directly affect the pulmonary barrier function. The detailed understanding of the pulmonary barrier including its architecture and functions is crucial for the diagnosis, prognosis, and therapeutic treatment strategies of pulmonary diseases. Thus, considering multiple side effects and limited efficacy of current therapeutic treatment strategies in patients with inflammatory diseases make experimental and models necessary to improving clinical therapy options. This review describes existing models for studyying the pulmonary barrier function under acute inflammatory conditions, which are meant to improve the translational approaches for outcome predictions, patient monitoring, and treatment decision-making.

KEYWORDS: 2D, 3D, ALI, LOAC, PCLS, air-liquid, co-culture, organoid

Publikations ID: 35874776
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