Journal article
Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury
JCI insight, Vol.7(23), 149955
12/08/2022
DOI: 10.1172/jci.insight.149955
PMCID: PMC9746901
PMID: 36264633
Abstract
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.
Details
- Title: Subtitle
- Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury
- Creators
- Filiz T. Korkmaz - University of Massachusetts Chan Medical SchoolAnukul T. Shenoy - Boston UniversityElise M. Symer - Boston UniversityLillia A. Baird - Boston UniversityChristine V. Odom - Boston UniversityEmad I. Arafa - Boston UniversityElim Na - Boston UniversityErnest L. Dimbo - Boston UniversityWilliam Molina-Arocho - Boston UniversityMatthew Brudner - Boston UniversityTheodore J. Standiford - University of Michigan–Ann ArborJawahar L. Mehta - Central Arkansas Veterans Healthcare SystemTatsuya Sawamura - Shinshu UniversityMatthew R. Jones - Boston UniversityJoseph P. Mizgerd - Boston UniversityKatrina E. Traber - Boston UniversityLee J. Quinton - University of Massachusetts Chan Medical School
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.7(23), 149955
- Publisher
- Amer Soc Clinical Investigation Inc
- DOI
- 10.1172/jci.insight.149955
- PMID
- 36264633
- PMCID
- PMC9746901
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Number of pages
- 23
- Grant note
- R01-HL111449; R01GM120060; R56-HL165718; T32-HL007035; F32-HL147461; K99-HL159258; R35-HL135756; R01-AI115053; F31-HL147397; K08-HL130582; R01-HL136725 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 12/08/2022
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984696757702771
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