ArticleThe Journal of clinical investigation2020
Epithelial membrane protein 2 governs transepithelial migration of neutrophils into the airspace.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
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- A recurrent de novo damaging variant inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- ALX/FPR2 Contributes to Serum Amyloid A-Induced Lung Neutrophil Recruitment Following Acute Ozone Exposure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Epigenetic profiles integrated with transcriptomic reveal the difference between COPD and PRISm in KOCOSS-NIH.Functional & integrative genomics · 2025Article
- GrB-Fc-KS49, an anti-EMP2 granzyme B fusion protein therapeutic alters immune cell infiltration and suppresses breast cancer growth.Journal for immunotherapy of cancer · 2024Article
- The Multifaceted Role of Epithelial Membrane Protein 2 in Cancer: from Biomarker to Therapeutic Target.Biomolecules & therapeutics · 2024Review
- Advances and Applications of Lung Organoids in the Research on Acute Respiratory Distress Syndrome (ARDS).Journal of clinical medicine · 2024Review
- Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis-induced injury.Immunity, inflammation and disease · 2023Article
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- Innate immune responses in pneumonia.Pneumonia (Nathan Qld.) · 2023Review
- Markers of immune dysregulation in response to the ageing gut: insights from aged murine gut microbiota transplants.BMC gastroenterology · 2022Article
- The underappreciated role of resident epithelial cell populations in metastatic progression: contributions of the lung alveolar epithelium.American journal of physiology. Cell physiology · 2022Review
- Unraveling the structures, functions and mechanisms of epithelial membrane protein family in human cancers.Experimental hematology & oncology · 2022Review
- New Insights into the Alveolar Epithelium as a Driver of Acute Respiratory Distress Syndrome.Biomolecules · 2022Review
- Nuclear receptor Nr1d1 alleviates asthma by abating GATA3 gene expression and Th2 cell differentiation.Cellular and molecular life sciences : CMLS · 2022Article
- Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2.Biomolecules & therapeutics · 2022Article
- Regulatory mechanisms of neutrophil migration from the circulation to the airspace.Cellular and molecular life sciences : CMLS · 2021Review
- Elevated postischemic tissue injury and leukocyte-endothelial adhesive interactions in mice with global deficiency in caveolin-2: role of PAI-1.American journal of physiology. Heart and circulatory physiology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Whether respiratory epithelial cells regulate the final transit of extravasated neutrophils into the inflamed airspace or are a passive barrier is poorly understood. Alveolar epithelial type 1 (AT1) cells, best known for solute transport and gas exchange, have few established immune roles. Epithelial membrane protein 2 (EMP2), a tetraspan protein that promotes recruitment of integrins to lipid rafts, is highly expressed in AT1 cells but has no known function in lung biology. Here, we show that Emp2-/- mice exhibit reduced neutrophil influx into the airspace after a wide range of inhaled exposures. During bacterial pneumonia, Emp2-/- mice had attenuated neutrophilic lung injury and improved survival. Bone marrow chimeras, intravital neutrophil labeling, and in vitro assays suggested that defective transepithelial migration of neutrophils into the alveolar lumen occurs in Emp2-/- lungs. Emp2-/- AT1 cells had dysregulated surface display of multiple adhesion molecules, associated with reduced raft abundance. Epithelial raft abundance was dependent upon putative cholesterol-binding motifs in EMP2, whereas EMP2 supported adhesion molecule display and neutrophil transmigration through suppression of caveolins. Taken together, we propose that EMP2-dependent membrane organization ensures proper display on AT1 cells of a suite of proteins required to instruct paracellular neutrophil traffic into the alveolus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.