Plasmalogens in Innate Immune Cells: From Arachidonate Signaling to Ferroptosis.

Polyunsaturated fatty acids such as arachidonic acid are indispensable components of innate immune signaling. Plasmalogens are glycerophospholipids with a vinyl ether bond in the sn-1 position of the glycerol backbone instead of the more common sn-1 ester bond present in "classical" glycerophospholipids. This kind of phospholipid is particularly rich in polyunsaturated fatty acids, especially arachidonic acid.

Rapid Movement of Palmitoleic Acid from Phosphatidylcholine to Phosphatidylinositol in Activated Human Monocytes.

This work describes a novel route for phospholipid fatty acid remodeling involving the monounsaturated fatty acid palmitoleic acid. When administered to human monocytes, palmitoleic acid rapidly incorporates into membrane phospholipids, notably into phosphatidylcholine (PC). In resting cells, palmitoleic acid remains within the phospholipid pools where it was initially incorporated, showing no further movement.

Implementation of a retinal stroke-code protocol results in visual recovery in patients receiving reperfusion therapies.

Introduction: Reperfusion therapies represent promising treatments for patients with Central Retinal Artery Occlusion (CRAO), but access is limited due to low incidence and lack of protocols. We aimed to describe the benefit of implementing a Retinal Stroke-Code protocol regarding access to reperfusion, visual acuity and aetiological assessment.

Patients And Methods: Prospective cohort study performed at a Comprehensive Stroke Centre.

Efficacy and safety of deep sclerectomy with uveoscleral implant plus collagen matrix implant overcoming the superficial scleral flap in glaucoma surgery.

Aim: To assess the efficacy and safety of non-penetrating deep sclerectomy (NPDS) with uveoscleral implant plus subconjunctival and intrascleral collagen matrix overcoming the superficial scleral flap lips (modified deep sclerectomy technique, DS) and minimal use of mitomycin C in glaucoma surgery.

Methods: A retrospective review of 47 consecutive glaucoma patients who underwent NPDS with DS between January 2017 and May 2018. Best-corrected visual acuity, intraocular pressure (IOP), post-operative need for glaucoma medications, visual field mean deviation (MD), re-interventions, needling revisions and laser goniopuncture were noted.

Dynamics of Docosahexaenoic Acid Utilization by Mouse Peritoneal Macrophages.

In this work, the incorporation of docosahexaenoic acid (DHA) in mouse resident peritoneal macrophages and its redistribution within the various phospholipid classes were investigated. Choline glycerophospholipids (PC) behaved as the major initial acceptors of DHA. Prolonged incubation with the fatty acid resulted in the transfer of DHA from PC to ethanolamine glycerophospholipids (PE), reflecting phospholipid remodeling.

Lipin-2 regulates the antiviral and anti-inflammatory responses to interferon.

Interferons (IFN) are crucial antiviral and immunomodulatory cytokines that exert their function through the regulation of a myriad of genes, many of which are not yet characterized. Here, we reveal that lipin-2, a phosphatidic acid phosphatase whose mutations produce an autoinflammatory syndrome known as Majeed syndrome in humans, is regulated by IFN in a STAT-1-dependent manner. Lipin-2 inhibits viral replication both in vitro and in vivo.

Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure.

Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs).

Birth, Expansion, and Contestation of Alcohol Per Se Laws: A Global Data Set of Policies Regulating Driving Under the Influence of Alcohol.

Objective: More than 270,000 people across the world die every year from alcohol-related crashes. Introducing alcohol per se laws (APL) based on a blood alcohol concentration (BAC) threshold of .05% could save at least 16,000 lives annually.

Differential Mobilization of the Phospholipid and Triacylglycerol Pools of Arachidonic Acid in Murine Macrophages.

Innate immune cells such as monocytes and macrophages contain high levels of arachidonic acid (AA), part of which can be mobilized during cellular activation for the formation of a vast array of bioactive oxygenated metabolites. Monocytes and macrophages present in inflammatory foci typically incorporate large amounts of AA, not only in membrane phospholipids, but also in neutral lipids such as triacylglycerol. Thus, it was of interest to investigate the metabolic fate of these two AA pools in macrophages.

Compartmentalized regulation of lipid signaling in oxidative stress and inflammation: Plasmalogens, oxidized lipids and ferroptosis as new paradigms of bioactive lipid research.

Perturbations in lipid homeostasis combined with conditions favoring oxidative stress constitute a hallmark of the inflammatory response. In this review we focus on the most recent results concerning lipid signaling in various oxidative stress-mediated responses and inflammation. These include phagocytosis and ferroptosis.

ISG15 Is a Novel Regulator of Lipid Metabolism during Infection.

Interferon-stimulated gene 15 (ISG15) is a 15-kDa ubiquitin-like modifier that binds to target proteins in a process termed ISGylation. ISG15, first described as an antiviral molecule against many viruses, participates in numerous cellular processes, from immune modulation to the regulation of genome stability. Interestingly, the role of ISG15 as a regulator of cell metabolism has recently gained strength.

Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer.

In the last few years, the monounsaturated hexadecenoic fatty acids are being increasingly considered as biomarkers of health with key functions in physiology and pathophysiology. Palmitoleic acid (16:1n-7) and sapienic acid (16:1n-10) are synthesized from palmitic acid by the action of stearoyl-CoA desaturase-1 and fatty acid desaturase 2, respectively. A third positional isomer, hypogeic acid (16:1n-9) is produced from the partial β-oxidation of oleic acid.

Phosphorylation of cPLAα at Ser Is Necessary for Its Translocation to PtdInsP-Enriched Membranes.

Group IVA cytosolic phospholipase Aα (cPLAα) is a key enzyme in physiology and pathophysiology because it constitutes a rate-limiting step in the pathway for the generation of pro- and anti-inflammatory eicosanoid lipid mediators. cPLAα activity is tightly regulated by multiple factors, including the intracellular Ca concentration, phosphorylation reactions, and cellular phosphatidylinositol (4,5) bisphosphate levels (PtdInsP). In the present work, we demonstrate that phosphorylation of the enzyme at Ser is an important step for the translocation of the enzyme to PtdInsP-enriched membranes in human cells.

Lipid Droplets, Phospholipase A, Arachidonic Acid, and Atherosclerosis.

Lipid droplets, classically regarded as static storage organelles, are currently considered as dynamic structures involved in key processes of lipid metabolism, cellular homeostasis and signaling. Studies on the inflammatory state of atherosclerotic plaques suggest that circulating monocytes interact with products released by endothelial cells and may acquire a foamy phenotype before crossing the endothelial barrier and differentiating into macrophages. One such compound released in significant amounts into the bloodstream is arachidonic acid, the common precursor of eicosanoids, and a potent inducer of neutral lipid synthesis and lipid droplet formation in circulating monocytes.

Lipin-1-derived diacylglycerol activates intracellular TRPC3 which is critical for inflammatory signaling.

Exposure to Gram-negative bacterial LPS exacerbates host immune responses and may lead to sepsis, a life-threatening condition. Despite its high mortality and morbidity, no drugs specifically directed to treating sepsis are currently available. Using human cell genetic depletion, pharmacological inhibition, live-cell microscopy and organelle-targeted molecular sensors we present evidence that the channel TRPC3 is activated intracellularly during macrophage exposure to LPS and is essential for Ca release from internal stores.

The Hypoxic Microenvironment Induces Stearoyl-CoA Desaturase-1 Overexpression and Lipidomic Profile Changes in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). It is characterized by a high cell proliferation and the ability to store lipids. Previous studies have demonstrated the overexpression of enzymes associated with lipid metabolism, including stearoyl-CoA desaturase-1 (SCD-1), which increases the concentration of unsaturated fatty acids in tumor cells.

Phospholipases: From Structure to Biological Function.

Phospholipases are enzymes that cleave ester bonds within phospholipids [...

Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLAα/COX-1 Pathway.

Macrophages are professional antigen presenting cells with intense phagocytic activity, strategically distributed in tissues and cavities. These cells are capable of responding to a wide variety of innate inflammatory stimuli, many of which are signaled by lipid mediators. The distribution of arachidonic acid (AA) among glycerophospholipids and its subsequent release and conversion into eicosanoids in response to inflammatory stimuli such as zymosan, constitutes one of the most studied models.

Release of Anti-Inflammatory Palmitoleic Acid and Its Positional Isomers by Mouse Peritoneal Macrophages.

Positional isomers of hexadecenoic acid are considered as fatty acids with anti-inflammatory properties. The best known of them, palmitoleic acid (cis-9-hexadecenoic acid, 16:1n-7), has been identified as a lipokine with important beneficial actions in metabolic diseases. Hypogeic acid (cis-7-hexadecenoic acid, 16:1n-9) has been regarded as a possible biomarker of foamy cell formation during atherosclerosis.

Phospholipid Arachidonic Acid Remodeling During Phagocytosis in Mouse Peritoneal Macrophages.

Macrophages contain large amounts of arachidonic acid (AA), which distributes differentially across membrane phospholipids. This is largely due to the action of coenzyme A-independent transacylase (CoA-IT), which transfers the AA primarily from diacyl choline-containing phospholipids to ethanolamine-containing phospholipids. In this work we have comparatively analyzed glycerophospholipid changes leading to AA mobilization in mouse peritoneal macrophages responding to either zymosan or serum-opsonized zymosan (OpZ).

A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase Aα.

Phospholipase As constitute a wide group of lipid-modifying enzymes which display a variety of functions in innate immune responses. In this work, we utilized mass spectrometry-based lipidomic approaches to investigate the action of Asp-49 Ca-dependent secreted phospholipase A (sPLA) (MT-III) and Lys-49 sPLA2 (MT-II), two group IIA phospholipase As isolated from the venom of the snake , on human peripheral blood monocytes. MT-III is catalytically active, whereas MT-II lacks enzyme activity.

The Contribution of Cytosolic Group IVA and Calcium-Independent Group VIA Phospholipase As to Adrenic Acid Mobilization in Murine Macrophages.

Adrenic acid (AA), the 2-carbon elongation product of arachidonic acid, is present at significant levels in membrane phospholipids of mouse peritoneal macrophages. Despite its abundance and structural similarity to arachidonic acid, very little is known about the molecular mechanisms governing adrenic acid mobilization in cells of the innate immune system. This contrasts with the wide availability of data on arachidonic acid mobilization.