Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury
Identifying host factors that contribute to pneumonia incidence and severity are of utmost importance to guiding the development of more effective therapies. Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, encoded by OLR1) is a scavenger receptor known to promote vascular injury and...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-12-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.149955 |
| _version_ | 1797634384050782208 |
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| author | Filiz T. Korkmaz Anukul T. Shenoy Elise M. Symer Lillia A. Baird Christine V. Odom Emad I. Arafa Ernest L. Dimbo Elim Na William Molina-Arocho Matthew Brudner Theodore J. Standiford Jawahar L. Mehta Tatsuya Sawamura Matthew R. Jones Joseph P. Mizgerd Katrina E. Traber Lee J. Quinton |
| author_facet | Filiz T. Korkmaz Anukul T. Shenoy Elise M. Symer Lillia A. Baird Christine V. Odom Emad I. Arafa Ernest L. Dimbo Elim Na William Molina-Arocho Matthew Brudner Theodore J. Standiford Jawahar L. Mehta Tatsuya Sawamura Matthew R. Jones Joseph P. Mizgerd Katrina E. Traber Lee J. Quinton |
| author_sort | Filiz T. Korkmaz |
| collection | DOAJ |
| description | Identifying host factors that contribute to pneumonia incidence and severity are of utmost importance to guiding the development of more effective therapies. Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, encoded by OLR1) is a scavenger receptor known to promote vascular injury and inflammation, but whether and how LOX-1 functions in the lung are unknown. Here, we provide evidence of substantial accumulation of LOX-1 in the lungs of patients with acute respiratory distress syndrome and in mice with pneumonia. Unlike previously described injurious contributions of LOX-1, we found that LOX-1 is uniquely protective in the pulmonary airspaces, limiting proteinaceous edema and inflammation. We also identified alveolar macrophages and recruited neutrophils as 2 prominent sites of LOX-1 expression in the lungs, whereby macrophages are capable of further induction during pneumonia and neutrophils exhibit a rapid, but heterogenous, elevation of LOX-1 in the infected lung. Blockade of LOX-1 led to dysregulated immune signaling in alveolar macrophages, marked by alterations in activation markers and a concomitant elevation of inflammatory gene networks. However, bone marrow chimeras also suggested a prominent role for neutrophils in LOX-1–mediated lung protection, further supported by LOX-1+ neutrophils exhibiting transcriptional changes consistent with reparative processes. Taken together, this work establishes LOX-1 as a tissue-protective factor in the lungs during pneumonia, possibly mediated by its influence on immune signaling in alveolar macrophages and LOX-1+ airspace neutrophils. |
| first_indexed | 2024-03-11T12:06:55Z |
| format | Article |
| id | doaj.art-b320f241dc9942bba46957a1d10f8c08 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:06:55Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-b320f241dc9942bba46957a1d10f8c082023-11-07T16:24:55ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-12-01723Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injuryFiliz T. KorkmazAnukul T. ShenoyElise M. SymerLillia A. BairdChristine V. OdomEmad I. ArafaErnest L. DimboElim NaWilliam Molina-ArochoMatthew BrudnerTheodore J. StandifordJawahar L. MehtaTatsuya SawamuraMatthew R. JonesJoseph P. MizgerdKatrina E. TraberLee J. QuintonIdentifying host factors that contribute to pneumonia incidence and severity are of utmost importance to guiding the development of more effective therapies. Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, encoded by OLR1) is a scavenger receptor known to promote vascular injury and inflammation, but whether and how LOX-1 functions in the lung are unknown. Here, we provide evidence of substantial accumulation of LOX-1 in the lungs of patients with acute respiratory distress syndrome and in mice with pneumonia. Unlike previously described injurious contributions of LOX-1, we found that LOX-1 is uniquely protective in the pulmonary airspaces, limiting proteinaceous edema and inflammation. We also identified alveolar macrophages and recruited neutrophils as 2 prominent sites of LOX-1 expression in the lungs, whereby macrophages are capable of further induction during pneumonia and neutrophils exhibit a rapid, but heterogenous, elevation of LOX-1 in the infected lung. Blockade of LOX-1 led to dysregulated immune signaling in alveolar macrophages, marked by alterations in activation markers and a concomitant elevation of inflammatory gene networks. However, bone marrow chimeras also suggested a prominent role for neutrophils in LOX-1–mediated lung protection, further supported by LOX-1+ neutrophils exhibiting transcriptional changes consistent with reparative processes. Taken together, this work establishes LOX-1 as a tissue-protective factor in the lungs during pneumonia, possibly mediated by its influence on immune signaling in alveolar macrophages and LOX-1+ airspace neutrophils.https://doi.org/10.1172/jci.insight.149955ImmunologyInflammation |
| spellingShingle | Filiz T. Korkmaz Anukul T. Shenoy Elise M. Symer Lillia A. Baird Christine V. Odom Emad I. Arafa Ernest L. Dimbo Elim Na William Molina-Arocho Matthew Brudner Theodore J. Standiford Jawahar L. Mehta Tatsuya Sawamura Matthew R. Jones Joseph P. Mizgerd Katrina E. Traber Lee J. Quinton Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury JCI Insight Immunology Inflammation |
| title | Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury |
| title_full | Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury |
| title_fullStr | Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury |
| title_full_unstemmed | Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury |
| title_short | Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury |
| title_sort | lectin like oxidized low density lipoprotein receptor 1 attenuates pneumonia induced lung injury |
| topic | Immunology Inflammation |
| url | https://doi.org/10.1172/jci.insight.149955 |
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