Liver-Dependent Lung Remodeling during Systemic Inflammation Shapes Responses to Secondary Infection

Odom, C.; Kim, Yuri; Burgess, Claire L.; Baird, Leemon C.; Korkmaz, Filiz; Na, Elim; Shenoy, A.T.; Arafa, E.I.; Lam, TuKiet T.; Jones, Matthew R.; Mizgerd, Joseph P.; Traber, K.; Quinton, Lee J.

doi:10.4049/jimmunol.2100254

Cited by 4 publications

(2 citation statements)

References 86 publications

(51 reference statements)

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“…Lungs were prepared for histology and immunofluorescence as previously described ( 57 , 58 ). Frozen sections (8 μM) were fixed, permeabilized with 0.2% Triton-X, and blocked with 10% donkey serum and 3% bovine serum albumin (blocking buffer).…”

Section: Methodsmentioning

confidence: 99%

Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury

Korkmaz¹,

Shenoy²,

Symer³

et al. 2022

JCI Insight

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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 lowdensity lipoprotein receptor-1 (LOX-1) is a scavenger receptor known to promote vascular injury and inflammation, but it is unknown whether and how LOX-1 functions in the lung. Here, we provide evidence of substantial accumulation of LOX-1 in the lungs of ARDS patients 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 two 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 (AMs) and LOX-1+ airspace neutrophils.

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Section: Methodsmentioning

confidence: 99%

Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury

Korkmaz¹,

Shenoy²,

Symer³

et al. 2022

JCI Insight

Self Cite

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show abstract

“…Meanwhile, the fluorescence was observed in the livers and spleens, whereas the signals in the hearts and kidneys were minimal ( Figure S3 A). Previous studies in mice demonstrated that pneumonia in the lung induces inflammatory response in liver ( Odom et al., 2021 ; Quinton et al., 2012 ). In addition, acute P. aeruginosa lung infections result in bacterial dissemination in blood and liver ( Pène et al., 2012 ; Gonçalves-de-Albuquerque et al., 2016 ; Ren et al., 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Neutrophil-mediated delivery of the combination of colistin and azithromycin for the treatment of bacterial infection

Gao

et al. 2022

iScience

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Extra-pulmonary control of respiratory defense

Korkmaz,

Quinton

2024

Cellular Immunology

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Liver-Dependent Lung Remodeling during Systemic Inflammation Shapes Responses to Secondary Infection

Cited by 4 publications

References 86 publications

Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury

Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury

Neutrophil-mediated delivery of the combination of colistin and azithromycin for the treatment of bacterial infection

Extra-pulmonary control of respiratory defense

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