Faculty Opinions recommendation of Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators.

Author(s):  
Bruce Levy ◽  
Jennifer Colby
Blood ◽  
2012 ◽  
Vol 120 (15) ◽  
pp. e60-e72 ◽  
Author(s):  
Jesmond Dalli ◽  
Charles N. Serhan

Abstract Phagocytes orchestrate acute inflammation and host defense. Here we carried out lipid mediator (LM) metabololipidomics profiling distinct phagocytes: neutrophils (PMN), apoptotic PMN, and macrophages. Efferocytosis increased specialized pro-resolving mediator (SPM) biosynthesis, including Resolvin D1 (RvD1), RvD2, and RvE2, which were further elevated by PMN microparticles. Apoptotic PMN gave elevated prostaglandin E2, lipoxin B4 and RvE2, whereas zymosan-stimulated PMN showed predominantly leukotriene B4 and 20-OH-leukotriene B4, as well as lipoxin marker 5,15-diHETE. Using deuterium-labeled precursors (d8-arachidonic acid, d5-eicosapentaenoic acid, and d5-docosahexaenoic acid), we found that apoptotic PMN and microparticles contributed to SPM biosynthesis during efferocytosis. M2 macrophages produced SPM including maresin-1 (299 ± 8 vs 45 ± 6 pg/2.5 × 105 cells; P < .01) and lower amounts of leukotriene B4 and prostaglandin than M1. Apoptotic PMN uptake by both macrophage subtypes led to modulation of their LM profiles. Leukotriene B4 was down-regulated in M2 (668 ± 81 vs 351 ± 39 pg/2.5 × 105 cells; P < .01), whereas SPM including lipoxin A4 (977 ± 173 vs 675 ± 167 pg/2.5 × 105 cells; P < .05) were increased. Conversely, uptake of apoptotic PMN by M2 macrophages reduced (∼ 25%) overall LM. Together, these results establish LM signature profiles of human phagocytes and related subpopulations. Moreover, they provide evidence for microparticle regulation of specific endogenous LM during defined stages of the acute inflammatory process and their dynamic changes in human primary phagocytes.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
L Rotheudt ◽  
E Moritz ◽  
M Markus ◽  
H Voelzke ◽  
N Friedrich ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction  Sphingosine-1-phosphate (S1P) is a lipid mediator of the immune system and vascular bed. However, cross-sectional analyses of S1P and parameters of vascular health in the population are sparse. Purpose  We explored the relation between S1P concentrations and several parameters of vascular health, i.e. ankle-brachial index (ABI), carotid intima-media thickness (cIMT), presence of carotid atherosclerotic plaques/stenosis, brachial artery flow-mediated dilation (FMD) as well as aortic wall thickness (AWT). Methods S1P was measured by liquid chromatography-tandem mass spectrometry in the population-based Study of Health in Pomerania (SHIP-TREND-0). ABI was calculated as the ratio of systolic blood pressure in arms and ankles. For cIMT, the distance between the lumen-intima and media-adventitia interfaces in longitudinal scans were measured. Carotid plaques were defined as a focal protrusion of the carotid vessel wall. Carotid stenosis was assessed with Doppler ultrasonography. FMD was evaluated by measuring the increase in brachial artery diameter after transient forearm ischemia. AWT was assessed by Magnetic Resonance Imaging.  Subjects with cancer, severe renal insufficiency, previous myocardial infarction and extreme values for S1P (&lt; 1st and &gt; 99th percentile) were excluded. Sex stratified linear regression models adjusted for age, smoking, waist-to-hip ratio and platelets were used to assess the relation between S1P and vascular disease parameters. Results A total of n = 3,643 participants (48% male, median age 51, 25th and 75th percentile 39 and 63 years) could be included in the analyses. The median S1P concentration was 0.788 µM (25th and 75th percentile 0.679 and 0.906, respectively). In men a 1 standard deviation higher S1P was associated with a significantly greater cIMT (β: 0.0057 95% confidence interval [CI]: 0.00027 to 0.0112 mm; p = 0.0396) and a lower ABI (β: -0.0090 (95% confidence interval [CI]: -0.0153 to -0.0029; p = 0.0038. In women S1P was significantly associated with cIMT (β: 0.0044 95% confidence interval [CI]: 0.0001 to 0.0086 mm; p = 0.0445) while no significant association was found for the relation of S1P with ABI. For both men and women S1P was not associated with FMD, the presence of carotid plaques/stenosis and AWT. Conclusions We found that S1P concentrations were positively related to a thicker cIMT in both sexes and lower ABI values in men. There was no association of S1P with any of the other vascular markers of interest. Future studies need to validate our results in other populations.


Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 801
Author(s):  
Maria Detopoulou ◽  
Agathi Ntzouvani ◽  
Filio Petsini ◽  
Labrini Gavriil ◽  
Εlizabeth Fragopoulou ◽  
...  

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.


2020 ◽  
Vol 22 (1) ◽  
pp. 384
Author(s):  
Pedro-Antonio Regidor ◽  
Anna Mueller ◽  
Manuela Sailer ◽  
Fernando Gonzalez Santos ◽  
Jose Miguel Rizo ◽  
...  

PCOS as the most common endocrine disorder of women in their reproductive age affects between 5–15% of the female population. Apart from its cardinal symptoms, like irregular and anovulatory cycles, hyperandrogenemia and a typical ultrasound feature of the ovary, obesity, and insulin resistance are often associated with the disease. Furthermore, PCOS represents a status of chronic inflammation with permanently elevated levels of inflammatory markers including IL-6 and IL-18, TNF-α, and CRP. Inflammation, as discovered only recently, consists of two processes occurring concomitantly: active initiation, involving “classical” mediators including prostaglandins and leukotrienes, and active resolution processes based on the action of so-called specialized pro-resolving mediators (SPMs). These novel lipid mediator molecules derive from the essential ω3-poly-unsaturated fatty acids (PUFAs) DHA and EPA and are synthesized via specific intermediates. The role and benefits of SPMs in chronic inflammatory diseases like obesity, atherosclerosis, and Diabetes mellitus has become a subject of intense research during the last years and since PCOS features several of these pathologies, this review aims at summarizing potential roles of SPMs in this disease and their putative use as novel therapeutics.


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