Endothelial Transcytosis in Acute Lung Injury: Emerging Mechanisms and Therapeutic Approaches
Acute Lung Injury (ALI) is characterized by widespread inflammation which in its severe form, Acute Respiratory Distress Syndrome (ARDS), leads to compromise in respiration causing hypoxemia and death in a substantial number of affected individuals. Loss of endothelial barrier integrity, pneumocyte...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.828093/full |
| _version_ | 1818307923836665856 |
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| author | Joshua H. Jones Richard D. Minshall Richard D. Minshall |
| author_facet | Joshua H. Jones Richard D. Minshall Richard D. Minshall |
| author_sort | Joshua H. Jones |
| collection | DOAJ |
| description | Acute Lung Injury (ALI) is characterized by widespread inflammation which in its severe form, Acute Respiratory Distress Syndrome (ARDS), leads to compromise in respiration causing hypoxemia and death in a substantial number of affected individuals. Loss of endothelial barrier integrity, pneumocyte necrosis, and circulating leukocyte recruitment into the injured lung are recognized mechanisms that contribute to the progression of ALI/ARDS. Additionally, damage to the pulmonary microvasculature by Gram-negative and positive bacteria or viruses (e.g., Escherichia coli, SARS-Cov-2) leads to increased protein and fluid permeability and interstitial edema, further impairing lung function. While most of the vascular leakage is attributed to loss of inter-endothelial junctional integrity, studies in animal models suggest that transendothelial transport of protein through caveolar vesicles, known as transcytosis, occurs in the early phase of ALI/ARDS. Here, we discuss the role of transcytosis in healthy and injured endothelium and highlight recent studies that have contributed to our understanding of the process during ALI/ARDS. We also cover potential approaches that utilize caveolar transport to deliver therapeutics to the lungs which may prevent further injury or improve recovery. |
| first_indexed | 2024-12-13T07:06:06Z |
| format | Article |
| id | doaj.art-c36dacf82e48424ca80a73d5274be188 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-13T07:06:06Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-c36dacf82e48424ca80a73d5274be1882022-12-21T23:55:49ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-03-011310.3389/fphys.2022.828093828093Endothelial Transcytosis in Acute Lung Injury: Emerging Mechanisms and Therapeutic ApproachesJoshua H. Jones0Richard D. Minshall1Richard D. Minshall2Department of Pharmacology, University of Illinois College of Medicine at Chicago, Chicago, IL, United StatesDepartment of Pharmacology, University of Illinois College of Medicine at Chicago, Chicago, IL, United StatesDepartment of Anesthesiology, University of Illinois College of Medicine at Chicago, Chicago, IL, United StatesAcute Lung Injury (ALI) is characterized by widespread inflammation which in its severe form, Acute Respiratory Distress Syndrome (ARDS), leads to compromise in respiration causing hypoxemia and death in a substantial number of affected individuals. Loss of endothelial barrier integrity, pneumocyte necrosis, and circulating leukocyte recruitment into the injured lung are recognized mechanisms that contribute to the progression of ALI/ARDS. Additionally, damage to the pulmonary microvasculature by Gram-negative and positive bacteria or viruses (e.g., Escherichia coli, SARS-Cov-2) leads to increased protein and fluid permeability and interstitial edema, further impairing lung function. While most of the vascular leakage is attributed to loss of inter-endothelial junctional integrity, studies in animal models suggest that transendothelial transport of protein through caveolar vesicles, known as transcytosis, occurs in the early phase of ALI/ARDS. Here, we discuss the role of transcytosis in healthy and injured endothelium and highlight recent studies that have contributed to our understanding of the process during ALI/ARDS. We also cover potential approaches that utilize caveolar transport to deliver therapeutics to the lungs which may prevent further injury or improve recovery.https://www.frontiersin.org/articles/10.3389/fphys.2022.828093/fullcaveolae (caveolin-1)endocytosisSrc signalingPV-1endothelial permeabilityacute lung injury |
| spellingShingle | Joshua H. Jones Richard D. Minshall Richard D. Minshall Endothelial Transcytosis in Acute Lung Injury: Emerging Mechanisms and Therapeutic Approaches Frontiers in Physiology caveolae (caveolin-1) endocytosis Src signaling PV-1 endothelial permeability acute lung injury |
| title | Endothelial Transcytosis in Acute Lung Injury: Emerging Mechanisms and Therapeutic Approaches |
| title_full | Endothelial Transcytosis in Acute Lung Injury: Emerging Mechanisms and Therapeutic Approaches |
| title_fullStr | Endothelial Transcytosis in Acute Lung Injury: Emerging Mechanisms and Therapeutic Approaches |
| title_full_unstemmed | Endothelial Transcytosis in Acute Lung Injury: Emerging Mechanisms and Therapeutic Approaches |
| title_short | Endothelial Transcytosis in Acute Lung Injury: Emerging Mechanisms and Therapeutic Approaches |
| title_sort | endothelial transcytosis in acute lung injury emerging mechanisms and therapeutic approaches |
| topic | caveolae (caveolin-1) endocytosis Src signaling PV-1 endothelial permeability acute lung injury |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.828093/full |
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