Lysophosphatidylcholine Alleviates Acute Lung Injury by Regulating Neutrophil Motility and Neutrophil Extracellular Trap Formation

Abstract

Sepsis is predominantly initiated by bacterial infection and can cause systemic inflammation, which frequently leads to rapid death of the patient. However, this acute systemic inflammatory response requires further investigation from the perspectives of clinical judgment criteria and early treatment strategies for the relief of symptoms. Lysophosphatidylcholine (LPC) 18:0 may relieve septic symptoms, but the relevant mechanism is not clearly understood. Therefore, we aimed to assess the effectiveness of LPC as a therapeutic treatment for acute inflammation in the lung induced by lipopolysaccharide in mice. Systemic inflammation of mice was induced by lipopolysaccharide (LPS) inoculation to investigate the role of LPC in the migration and the immune response of neutrophils during acute lung injury. By employing two-photon intravital imaging of the LPS-stimulated LysM-GFP mice and other in vitro and in vivo assays, we examined whether LPC alleviates the inflammatory effect of sepsis. We also tested the effect of LPC to human neutrophils from healthy control and sepsis patients. Our data showed that LPC treatment reduced the infiltration of innate immune cells into the lung. Specifically, LPC altered neutrophil migratory patterns and enhanced phagocytic efficacy in the damaged lung. Moreover, LPC treatment reduced the release of neutrophil extracellular trap (NET), which can damage tissue in the inflamed organ and exacerbate disease. It also reduced human neutrophil migration under inflammatory environment. Our results suggest that LPC can alleviate sepsis-induced lung inflammation by regulating the function of neutrophils. These findings provide evidence for the beneficial application of LPC treatment as a potential therapeutic strategy for sepsis.

Developing A Baseline Metabolomic Signature Associated with COVID-19 Severity: Insights from Prospective Trials Encompassing 13 U.S. Centers

“…However, the effect of LysoPC molecules on inflammation remains controversial. Both proinflammatory [23,25] and anti-inflammatory [26][27][28][29][30][31][32] effects of the LysoPC molecules have been reported previously. Our results are in agreement with other studies showing that LysoPC levels are lower in patients with more severe COVID-19 [26,28,29].…”

The effects of live and pasteurized Akkermansia muciniphila on DSS-induced ulcerative colitis, gut microbiota, and metabolomics in mice

“…34 LysoPC (18 : 0) can reduce inflammation by decreasing pro-inflammatory cytokines and increasing anti-inflammatory cytokines. 35,36 Specifically, we found that Parasutterella and Akkermansia were positively associated with LysoPE (18 : 0/ 0 : 0), LysoPC (20 : 3(5Z,8Z,11Z)), LysoPC (20 : 1(11Z)), LysoPC (20 : 2(11Z,14Z)) and LysoPC (P-18:0). Therefore, we hypothesized that A. muciniphila activates organismal immunity by increasing the abundance of Parasutterella and Akkermansia, thus affecting the metabolism of lipid and lipid-like molecules associated with LysoPCs and LysoPE, which is beneficial for the relief of colitis in mice.…”

Patients with Bacterial Sepsis Are Heterogeneous with Regard to Their Systemic Lipidomic Profiles

“…First, lysophosphatidylcholines can increase neutrophil adhesion, increase the expression of the CD11b adhesion molecule expression and increase the expression of pro-chemotactic receptors for formylated peptides [ 24 ]; local neutrophil infiltration is thereby increased [ 25 ]. These metabolites also have the potential to increase neutrophil degranulation [ 24 ], increase neutrophil bactericidal activity [ 26 ], and regulate extracellular trap formation [ 27 ]. Lysophosphatidylcholines can bind to the G-protein coupled G2A receptors and thereby initiate intracellular signaling and enhance the pro-inflammatory functions of both neutrophils [ 28 ] and monocytes/macrophages [ 29 , 30 ].…”