scholarly journals Effect of cooling on lung secretory phospholipase A2 activity in vitro, ex vivo, and in vivo

2019 ◽  
Vol 316 (3) ◽  
pp. L498-L505 ◽  
Author(s):  
Chiara Autilio ◽  
Shivani Shankar-Aguilera ◽  
Angelo Minucci ◽  
Lhoussaine Touqui ◽  
Daniele De Luca
Keyword(s):  
Bronchoalveolar Lavage ◽  
Phospholipase A2 ◽  
Bile Acids ◽  
Ex Vivo ◽  
Whole Body ◽  
Secretory Phospholipase A2 ◽  
Secretory Phospholipase ◽  
Spla2 Activity

Hypothermia can modify surfactant composition and function. Secretory phospholipase A2 (sPLA2) hydrolyses surfactant phospholipids and is important in the pathobiology of several critical respiratory disorders. We hypothesize that sPLA2 activity might be influenced by the temperature partially explaining surfactant changes. This study aims to evaluate comprehensively the effect of hypothermia on sPLA2 activity. We measured sPLA2 activity at different temperatures, alone or combined with bile acids, in vitro (incubating human recombinant sPLA2-IIA and porcine sPLA2-IB), ex vivo (by cooling bronchoalveolar lavage samples from neonates with respiratory distress syndrome or no lung disease), and in vivo (using lavage samples obtained before and after 72 h of whole body cooling in neonates with hypoxic-ischemic encephalopathy). We also measured concentrations of various sPLA2 subtypes and natural sPLA2 inhibitors in in vivo cooled samples. Results were corrected for protein content and dilution. In vitro cooling did not show any effect of hypothermia on sPLA2. Ex vivo cooling did not alter total sPLA2 activity, and the addition of bile acids increased sPLA2 activity irrespective of the temperature and the type of sampled patient. In vivo hypothermia reduced median sPLA2 activity from 16.6 [15.2–106.7] IU/mg to 3.3 [2.7–8.5] IU/mg ( P = 0.026) and mean sPLA2-IIA from 1.1 (0.8) pg/μg to 0.6 (0.4) pg/μg ( P = 0.047), whereas dioleylphosphatidylglycerol increased from 8.3 (3.9)% to 12.8 (5.1)% ( P = 0.02). Whole body hypothermia decreases in vivo global sPLA2 activity in bronchoalveolar lavage fluids through the reduction of sPLA2-IIA and increment of dioleylphosphatidylglycerol. This effect is absent during in vitro or ex vivo hypothermia.

scholarly journals Secretory Phospholipase A2 Tipe Ii (Spla Ii) pada Penyakit Kardiovaskuler

2015 ◽  
pp. 271-9
Author(s):  
Djanggan Sargowo
Keyword(s):  
Phospholipase A2 ◽  
Secretory Phospholipase A2 ◽  
Secretory Phospholipase

Reaksi inflamasi berperan dalam beberapa pathogenesis kondisi kardiovaskuler seperti atherosklerosis dan kerusakan iskemikpada infark miokard akut (IMA). Di antara mediator-mediator yang terlibat dalam inflamasi tersebut adalah enzim secretoryphospholipase A2 tipe II (sPLA2-II). Meskipun beberapa sel memang memproduksi sPLA2-II, namun sintesis oleh sel-sel tertentuseperti hepatosit, adalah khas sebagai reaktan fase akut. Literatur terbaru menyatakan banyaknya peran dari sPLA2-II dalampenyakit kardiovaskuler. Dalam tulisan berikut, akan mendiskusikan peran sPLA2-II dalam berbagai model atherosklerosisatau IMA, baik in vitro maupun in vivo, termasuk perspektif terapeutik dari sPLA2-II inhibitor. Disimpulkan bahwa sPLA2-IImerupakan mediator inflamasi yang penting dalam penyakit kardiovaskuler.

scholarly journals Knockdown of secretory phospholipase A2 IIa reduces lung cancer growth in vitro and in vivo

2012 ◽  
Vol 144 (5) ◽  
pp. 1185-1191 ◽  
Author(s):  
Jessica A. Yu ◽  
David Mauchley ◽  
Howard Li ◽  
Xianzhong Meng ◽  
Raphael A. Nemenoff ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phospholipase A2 ◽  
Cancer Growth ◽  
Secretory Phospholipase A2 ◽  
Secretory Phospholipase

scholarly journals IMMU-31. QUANTITATIVE EVALUATION OF ROUTES OF ADMINISTRATION OF IMMUNOTHERAPEUTIC T CELLS TO ORTHOTOPIC GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii111-ii111
Author(s):  
Lan Hoang-Minh ◽  
Angelie Rivera-Rodriguez ◽  
Fernanda Pohl-Guimarães ◽  
Seth Currlin ◽  
Christina Von Roemeling ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Ex Vivo ◽  
Adoptive T Cell Therapy ◽  
Whole Body ◽  
T Cell Therapy ◽  
Clinical Responses

Abstract SIGNIFICANCE Adoptive T cell therapy (ACT) has emerged as the most effective treatment against advanced malignant melanoma, eliciting remarkable objective clinical responses in up to 75% of patients with refractory metastatic disease, including within the central nervous system. Immunologic surrogate endpoints correlating with treatment outcome have been identified in these patients, with clinical responses being dependent on the migration of transferred T cells to sites of tumor growth. OBJECTIVE We investigated the biodistribution of intravenously or intraventricularly administered T cells in a murine model of glioblastoma at whole body, organ, and cellular levels. METHODS gp100-specific T cells were isolated from the spleens of pmel DsRed transgenic C57BL/6 mice and injected intravenously or intraventricularly, after in vitro expansion and activation, in murine KR158B-Luc-gp100 glioma-bearing mice. To determine transferred T cell spatial distribution, the brain, lymph nodes, heart, lungs, spleen, liver, and kidneys of mice were processed for 3D imaging using light-sheet and multiphoton imaging. ACT T cell quantification in various organs was performed ex vivo using flow cytometry, 2D optical imaging (IVIS), and magnetic particle imaging (MPI) after ferucarbotran nanoparticle transfection of T cells. T cell biodistribution was also assessed in vivo using MPI. RESULTS Following T cell intravenous injection, the spleen, liver, and lungs accounted for more than 90% of transferred T cells; the proportion of DsRed T cells in the brains was found to be very low, hovering below 1%. In contrast, most ACT T cells persisted in the tumor-bearing brains following intraventricular injections. ACT T cells mostly concentrated at the periphery of tumor masses and in proximity to blood vessels. CONCLUSIONS The success of ACT immunotherapy for brain tumors requires optimization of delivery route, dosing regimen, and enhancement of tumor-specific lymphocyte trafficking and effector functions to achieve maximal penetration and persistence at sites of invasive tumor growth.

Varespladib Inhibits Secretory Phospholipase A2 in Bronchoalveolar Lavage of Different Types of Neonatal Lung Injury

2012 ◽  
Vol 52 (5) ◽  
pp. 729-737 ◽  
Author(s):  
Daniele De Luca ◽  
Angelo Minucci ◽  
Joaquim Trias ◽  
Domenico Tripodi ◽  
Giorgio Conti ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Phospholipase A2 ◽  
Secretory Phospholipase A2 ◽  
Secretory Phospholipase ◽  
Different Types ◽  
Neonatal Lung ◽  
Neonatal Lung Injury

Detection of allergen-induced airway hyperresponsiveness in isolated mouse lungs

2006 ◽  
Vol 291 (3) ◽  
pp. L466-L472 ◽  
Author(s):  
Martin Witzenrath ◽  
Birgit Ahrens ◽  
Stefanie M. Kube ◽  
Armin Braun ◽  
Heinz G. Hoymann ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Ex Vivo ◽  
Whole Body ◽  
Strongly Correlated ◽  
Ex Vivo Model ◽  
Isolated Lungs ◽  
Spontaneously Breathing

Airway hyperresponsiveness (AHR) is a hallmark of bronchial asthma. Important features of this exaggerated response to bronchoconstrictive stimuli have mostly been investigated in vivo in intact animals or in vitro in isolated tracheal or bronchial tissues. Both approaches have important advantages but also certain limitations. Therefore, the aim of our study was to develop an ex vivo model of isolated lungs from sensitized mice for the investigation of airway responsiveness (AR). BALB/c mice were sensitized by intraperitoneal ovalbumin (Ova) and subsequently challenged by Ova inhalation. In vivo AR was measured in unrestrained animals by whole body plethysmography after stimulation with aerosolized methacholine (MCh) with determination of enhanced pause ( Penh). Twenty-four hours after each Penh measurement, airway resistance was continuously registered in isolated, perfused, and ventilated lungs on stimulation with inhaled or intravascular MCh or nebulized Ova. In a subset of experiments, in vivo AR was additionally measured in orotracheally intubated, spontaneously breathing mice 24 h after Penh measurement, and lungs were isolated further 24 h later. Isolated lungs of allergen-sensitized and -challenged mice showed increased AR after MCh inhalation or infusion as well as after specific provocation with aerosolized allergen. AR was increased on days 2 and 5 after Ova challenge and had returned to baseline on day 9. AHR in isolated lungs after aerosolized or intravascular MCh strongly correlated with in vivo AR. Pretreatment of isolated lungs with the β2-agonist fenoterol diminished AR. In conclusion, this model provides new opportunities to investigate mechanisms of AHR as well as pharmacological interventions on an intact organ level.

scholarly journals Direct anabolic three carbon metabolism via propionate to a six carbon metabolite occurs in human heart and in vivo across mouse tissues

2019 ◽  
Author(s):  
Mary T. Doan ◽  
Michael D. Neinast ◽  
Erika L Varner ◽  
Kenneth Bedi ◽  
David Bartee ◽  
...  
Keyword(s):  
Human Heart ◽  
Ex Vivo ◽  
Tibialis Anterior Muscle ◽  
Whole Body ◽  
List Type ◽  
Isotope Tracing ◽  
Brown Adipose ◽  
Mouse Tissues

AbstractAnabolic metabolism of carbon in mammals is mediated via the one and two carbon carriers S-adenosyl methionine and acetyl-coenzyme A (acetyl-CoA). In contrast, anabolic metabolism using three carbon units via propionate is not thought to occur. Mammals are primarily thought to oxidize the 3-carbon short chain fatty acid propionate by shunting propionyl-CoA to succinyl-CoA for entry into the TCA cycle. We found that this may not be absolute and that in mammals one non-oxidative fate of two units of propionyl-CoA is to condense to a six-carbon trans-2-methyl-2-pentenoyl-CoA (2M2PE-CoA). We confirmed this pathway using purified protein extracts provided limited substrates and confirmed the product with a synthetic standard. In whole-body in vivo stable isotope tracing with infusion of 13C-labeled valine achieving steady state, 2M2PE-CoA formed via propionyl-CoA in multiple murine tissues including heart, kidney, and to a lesser degree in brown adipose tissue, liver, and tibialis anterior muscle. Using ex vivo isotope tracing, we found that 2M2PE-CoA formed in human myocardial tissue incubated with propionate to a limited extent. While the complete enzymology of this pathway remains to be elucidated, these results confirm the in vivo existence of at least one anabolic three to six carbon reaction conserved in humans and mice that utilizes three carbons via propionate.Highlights- Synthesis and confirmation of structure 2-methyl-2-pentenoyl-CoA- In vivo fate of valine across organs includes formation of a 6-carbon metabolite from propionyl-CoA- Ex vivo metabolism of propionate in the human heart includes direct anabolism to a 6-carbon product- In both cases, this reaction occurred at physiologically relevant concentrations of propionate and valine- In vitro this pathway requires propionyl-CoA and NADH/NADPH as substrates

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