Postinjury serum secretory phospholipase A2 correlates with hypoxemia and clinical status at 72 hours

Neidlinger, Nikole; Hirvela, Elsa R.; Skinner, Ruby; Larkin, Sandra; Harken, Alden H.; Kuypers, Frans A.

doi:10.1016/j.jamcollsurg.2004.10.010

Cited by 23 publications

(21 citation statements)

References 20 publications

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“…1). The concentrations of sPLA 2 that hydrolyzed PS-exposing red blood cells are similar to sPLA 2 concentrations reported in sera of trauma and septic patients (7,8,10). Flow cytometric analysis confirmed the loss of PS-exposing cells after sPLA 2 incubation.…”

Section: Methodssupporting

confidence: 76%

“…In addition, it has been well established that bacterial membranes are excellent substrates for this enzyme (6). Together, membranes with altered phospholipid packing are potential targets for sPLA 2 type IIa.We have previously shown that sPLA 2 is elevated after injury, predicts hypoxemia, and is related to multiorgan failure (7,8). In addition, elevated levels of sPLA 2 predict the onset of the acute chest syndrome in sickle cell disease (9 -11), the severe lung damage that is a major cause of death in these patients.…”

mentioning

confidence: 99%

“…We have previously shown that sPLA 2 is elevated after injury, predicts hypoxemia, and is related to multiorgan failure (7,8). In addition, elevated levels of sPLA 2 predict the onset of the acute chest syndrome in sickle cell disease (9 -11), the severe lung damage that is a major cause of death in these patients.…”

mentioning

confidence: 99%

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Hydrolysis of Phosphatidylserine-exposing Red Blood Cells by Secretory Phospholipase A2 Generates Lysophosphatidic Acid and Results in Vascular Dysfunction

Neidlinger

Larkin²,

Bhagat³

et al. 2006

Journal of Biological Chemistry

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101

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Secretory phospholipase A 2 (sPLA 2 ) type IIa, elevated in inflammation, breaks down membrane phospholipids and generates arachidonic acid. We hypothesized that sPLA 2 will hydrolyze red blood cells that expose phosphatidylserine (PS) and generate lysophosphatidic acid (LPA) from phosphatidic acid that is elevated in PS-exposing red blood cells. In turn, LPA, a powerful lipid mediator, could affect vascular endothelial cell function. Although normal red blood cells were not affected by sPLA 2 , at levels of sPLA 2 observed under inflammatory conditions (100 ng/ml) PS-exposing red blood cells hemolyzed and generated LPA (1.2 nM/10 8 RBC). When endothelial cell monolayers were incubated in vitro with LPA, a loss of confluence was noted. Moreover, a dose-dependent increase in hydraulic conductivity was identified in rat mesenteric venules in vivo with 5 M LPA, and the combination of PS-exposing red blood cells with PLA 2 caused a similar increase in permeability. In the presence of N-palmitoyl L-serine phosphoric acid, a competitive inhibitor for the endothelial LPA receptor, loss of confluence in vitro and the hydraulic permeability caused by 5 M LPA in vivo were abolished. The present study demonstrates that increased sPLA 2 activity in inflammation in the presence of cells that have lost their membrane phospholipid asymmetry can lead to LPA-mediated endothelial dysfunction and loss of vascular integrity.Secretory phospholipase A 2 (sPLA 2 ) 2 type IIa is a low molecular weight, ubiquitous enzyme that is elevated in inflammation. The enzyme generates arachidonic acid from phospholipids for the generation of thromboxanes and leukotrienes and, as such, acts as an essential mediator in the inflammatory pathways (1). The specific membranes targeted by the enzyme for the generation of arachidonic acid during inflammation have not been clearly defined. Secretory PLA 2 has a strong preference for phospholipids that are negatively charged at physiologic pH: phosphatidylserine (PS) and phosphatidylethanolamine (PE) (2). In normal mammalian cells, these phospholipids are mainly (PE) or exclusively (PS) confined to the inner layer of the plasma membrane (1-3). Loss of this asymmetric distribution and exposure of PS on the external surface generates a thrombogenic surface and signals macrophages to remove cells by phagocytosis (1-5). Although normal mammalian cells do not seem to act as targets for sPLA 2 , loss of phospholipid asymmetry in plasma membranes and the exposure of PS have been shown to render them vulnerable to phospholipid hydrolysis (1). In addition, it has been well established that bacterial membranes are excellent substrates for this enzyme (6). Together, membranes with altered phospholipid packing are potential targets for sPLA 2 type IIa.We have previously shown that sPLA 2 is elevated after injury, predicts hypoxemia, and is related to multiorgan failure (7,8). In addition, elevated levels of sPLA 2 predict the onset of the acute chest syndrome in sickle cell disease (9 -11), the severe lung damage that...

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Section: Methodssupporting

confidence: 76%

mentioning

confidence: 99%

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Hydrolysis of Phosphatidylserine-exposing Red Blood Cells by Secretory Phospholipase A2 Generates Lysophosphatidic Acid and Results in Vascular Dysfunction

Neidlinger

Larkin²,

Bhagat³

et al. 2006

Journal of Biological Chemistry

Self Cite

101

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“…The primary source of free radical generation in cells during hypoxia has been reported to be a decrease in mitochondria redox potential causing reactive oxygen species (ROS) production from the electron transport chain (ETC), mainly at the level of cytochrome III (Guzy and Schumacker 2006). In addition, oxygen radical release might be enhanced during hypoxic conditions by the activation of xanthine oxidase (Sohn et al 2003), NAPDH-oxidase (Jones et al 2000) and phospholipase A 2 (Neidlinger et al 2005). Such an association during LHTL training (i.e., physical exercises and bouts of hypoxia) could affect the prooxidant/antioxidant balance.…”

Section: Introductionmentioning

confidence: 99%

Thirteen days of “live high–train low” does not affect prooxidant/antioxidant balance in elite swimmers

Pialoux¹,

Mounier²,

Brugniaux³

et al. 2009

Eur J Appl Physiol

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We investigated the impact of 13 days of "living high-training low" (LHTL) on the antioxidant/prooxidant balance in elite endurance swimmers. Eighteen elite swimmers from the French Swimming Federation were submitted to a 13-day endurance training and divided into two groups: one group trained at 1,200 m and lived in hypoxia (2,500-3,000 m simulated altitude) and the second group trained and lived at 1,200 m. The subjects performed an acute hypoxic test (10 min at 4,800 m) before and 1 day after the training period. Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA), ferric reducing antioxidant power (FRAP), and lipid-soluble antioxidants were measured before and after the 4,800 m tests. After the training, MDA and AOPP responses to the 4,800 m test were lower than before training for both groups (+10 vs. +2%; P = 0.01 for MDA and +80 vs. +14%; P = 0.01 for AOPP). Thirteen days of LHTL did not modify antioxidant status (FRAP and lipid-soluble antioxidants) despite intakes in vitamins A and E below the recommended daily allowances. The LHTL did not affect the antioxidant status in elite swimmers; however, the normoxic endurance training induced preconditioning mechanisms in response to the 4,800 m test.

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“…MPs derived from monocytes and endothelial cells express tissue factor (Shet et al 2003); once coagulation cascade is initiated by tissue factor, thrombin generation is greatly accelerated in the presence of PS (Zwaal and Schroit 1997;Mann 1999;Setty et al 2001). Moreover, hydrolysis of PS by secretory phospholipase A2 leads to generation of vasoactive prostaglandins, leukotrienes, and thromboxanes (Neidlinger et al 2005(Neidlinger et al , 2006.…”

Section: Introductionmentioning

confidence: 99%

Impact of circulating erythrocyte-derived microparticles on coagulation activation in sickle cell disease

et al. 2014

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Sickle cell disease (SCD) is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and the presence of circulating cell-derived microparticles (MPs). The aim of this work was to study the impact of erythrocyte-derived circulating microparticles (glycophorin A; CD235 positive) on coagulation activation and their probable role in contribution to painful crisis in SCD patients. Peripheral blood samples of 25 SCD patients during painful crisis and in steady state were studied for the presence of erythrocyte-derived MPs using flow cytometry. Estimation of D-dimer level, as a marker of coagulation activation, was done using semiquantitative assay. Thirty-six healthy individuals, age-and sex-matched, were included as a control group. Erythrocyte-derived MPs level was significantly higher in SCD patients during painful crisis compared to control group (p=0.02), but no statistically significant difference was found between erythrocyte-derived MPs level in SCD patients in steady state compared to controls or to SCD patients during painful crisis (p=0.3 and 0.49, respectively). D-dimer level was higher in SCD patients both during crisis and in steady state compared to controls (p<0.001). SCD during painful crisis is associated with increased levels of erythrocytederived MPs and D-dimer which may contribute to the hypercoagulable state observed in such group of patients.

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Postinjury serum secretory phospholipase A2 correlates with hypoxemia and clinical status at 72 hours

Cited by 23 publications

References 20 publications

Hydrolysis of Phosphatidylserine-exposing Red Blood Cells by Secretory Phospholipase A2 Generates Lysophosphatidic Acid and Results in Vascular Dysfunction

Hydrolysis of Phosphatidylserine-exposing Red Blood Cells by Secretory Phospholipase A2 Generates Lysophosphatidic Acid and Results in Vascular Dysfunction

Thirteen days of “live high–train low” does not affect prooxidant/antioxidant balance in elite swimmers

Impact of circulating erythrocyte-derived microparticles on coagulation activation in sickle cell disease

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