12-hydroxy-5-8-10-14-eicosatetraenoic-acid and Acute-Lung-Injury

Resident-tissue macrophages (RTMs) arise from embryonic precursors

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Lung Injury; Animals; Animals, Newborn; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Cell Self Renewal; COVID-19; Disease Susceptibility; Influenza A virus; Lipopolysaccharides; Lung; Macrophages, Alveolar; Mice; Neutrophils; Orthomyxoviridae Infections; Prostaglandins E; SARS-CoV-2

The accumulation of non-polar lipids arachidonic acid, 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE and 15-HETE during storage of transfusion products may play a role in the onset of transfusion-related acute lung injury (TRALI), a syndrome of respiratory distress after transfusion.. We investigated non-polar lipid accumulation in red blood cells (RBCs) stored for 42 days, plasma stored for 7 days at either 4 or 20°C and platelet (PLT) transfusion products stored for 7 days. Furthermore, we investigated whether transfusion of RBCs with increased levels of non-polar lipids induces TRALI in a 'two-hit' human volunteer model. All products were produced following Dutch Blood Bank protocols and are according to European standards. Non-polar lipids were measured with high-performance liquid chromotography followed by mass spectrometry.. All non-polar lipids increased in RBCs after 21 days of storage compared to baseline. The non-polar lipid concentration in plasma increased significantly, and the increase was even more pronounced in products stored at 20°C. In platelets, baseline levels of 5-HETE and 15-HETE were higher than in RBCs or plasma. However, the non-polar lipids did not change significantly during storage of PLT products. Infusion of RBCs with increased levels of non-polar lipids did not induce TRALI in LPS-primed human volunteers.. We conclude that non-polar lipids accumulate in RBC and plasma transfusion products and that accumulation is temperature dependent. Accumulation of non-polar lipids does not appear to explain the onset of TRALI (Dutch Trial Register - NTR4455).

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Lung Injury; Adolescent; Adult; Arachidonic Acid; Blood Platelets; Blood Preservation; Blood Transfusion, Autologous; Chromatography, High Pressure Liquid; Erythrocytes; Humans; Hydroxyeicosatetraenoic Acids; Lipids; Lipopolysaccharides; Male; Models, Theoretical; Platelet Transfusion; Registries; Tandem Mass Spectrometry; Temperature; Time Factors; Transfusion Reaction; Young Adult

We previously reported that the cytochrome P450 product 20-hydroxyeicosatetraenoic acid has prosurvival effects in pulmonary artery endothelial cells and ex vivo pulmonary arteries. We tested the potential of a 20-hydroxyeicosatetraenoic acid analog N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (20-5,14-HEDGE) to protect against lung ischemic reperfusion injury in rats. Furthermore, we examined activation of innate immune system components, high mobility group box 1 (HMGB1) and toll-like receptor 4 (TLR4), in this model as well as the effect of 20-5,14-HEDGE on this signaling pathway.. Sprague-Dawley rats treated with 20-5,14-HEDGE or vehicle were subjected to surgically induced, unilateral lung ischemia for 60 minutes followed by reperfusion for 2 hours in vivo. Injury was assessed histologically by hematoxylin and eosin, and with identification of myeloperoxidase immunohistochemically. The HMGB1 and TLR4 proteins were identified by Western blot. Caspase 3 activity or 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole, incorporation were used to measure apoptosis and cell survival.. The ischemia reperfusion injury evoked atelectasis and hemorrhage, an influx of polymorphonuclear cells, and increased TLR4 and HMGB1 expression. Caspase 3 activity was increased, and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide incorporation was decreased. The 20-5,14-HEDGE protected against each of these endpoints, including infiltration of polymorphonuclear cells, with no changes in caspase 3 activity in other organs.. Lung ischemia reperfusion produces apoptosis and activation of the innate immune system including HMGB1 and TLR4 within 2 hours of reperfusion. Treatment with 20-5,14-HEDGE decreases activation of this response system, and salvages lung tissue.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Lung Injury; Animals; Apoptosis; Caspase 3; Disease Models, Animal; HMGB1 Protein; Lipopeptides; Lung; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4

Acute lung injury (ALI) is a prevalent disease associated with high mortality. 12/15-lipoxygenase (12/15-LO) is an enzyme producing 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE from arachidonic acid. To test whether 12/15-LO is involved in increasing vascular permeability in the lung, we investigated the role of 12/15-LO in murine models of LPS-induced pulmonary inflammation and clinically relevant acid-induced ALI. The vascular permeability increase upon LPS inhalation was abolished in Alox15(-/-) mice lacking 12/15-LO and in wild-type mice after pharmacological blockade of 12/15-LO. Alox15(-/-) mice also showed improved gas exchange, reduced permeability increase, and prolonged survival in the acid-induced ALI model. Bone marrow chimeras and reconstitution experiments revealed that 12-HETE produced by hematopoietic cells regulates vascular permeability through a CXCR2-dependent mechanism. Our findings suggest that 12/15-LO-derived 12-HETE is a key mediator of vascular permeability in acute lung injury.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Lung Injury; Animals; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Caffeic Acids; Capillary Permeability; Cells, Cultured; Disease Models, Animal; Humans; Inflammation Mediators; Lipopolysaccharides; Lipoxygenase Inhibitors; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Microcirculation; Multienzyme Complexes; Survival Analysis