Sera of patients suffering from inflammatory diseases contain group IIA but not group V phospholipase A2

Aarsman, A.J.; Neys, F.W.; Helm, Hester A. van der; Kuypers, Frans A.; Bosch, H. van den

doi:10.1016/s0925-4439(00)00050-8

Cited by 18 publications

(9 citation statements)

References 36 publications

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“…The addition of respiratory substrates increases membrane potential and reduces the release of the enzyme in the extramitochondrial medium. The released PLA 2 has properties identical to those reported for type IIA secreted enzyme isolated from other cells or fluids (20,66,67) and immunoreacts with monoclonal antibody raised against rat liver mitochondrial sPLA 2 (68).…”

Section: Discussionsupporting

confidence: 59%

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Macchioni¹,

Corazzi²,

Nardicchi³

et al. 2004

Journal of Biological Chemistry

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Activation of brain mitochondrial phospholipase(s) A 2 (PLA 2 ) might contribute to cell damage and be involved in neurodegeneration. Despite the potential importance of the phenomenon, the number, identities, and properties of these enzymes are still unknown. Here, we demonstrate that isolated mitochondria from rat brain cortex, incubated in the absence of respiratory substrates, release a Ca 2؉ -dependent PLA 2 having biochemical properties characteristic to secreted PLA 2 (sPLA 2 ) and immunoreacting with the antibody raised against recombinant type IIA sPLA 2 (sPLA 2 -IIA). Under identical conditions, no release of fumarase in the extramitochondrial medium was observed. The release of sPLA 2 from mitochondria decreases when mitochondria are incubated in the presence of respiratory substrates such as ADP, malate, and pyruvate, which causes an increase of transmembrane potential determined by cytofluorimetric analysis using DiOC 6 (3) as a probe. The treatment of mitochondria with the uncoupler carbonyl cyanide 3-chlorophenylhydrazone slightly enhances sPLA 2 release. The increase of sPLA 2 specific activity after removal of mitochondrial outer membrane indicates that the enzyme is associated with mitoplasts. The mitochondrial localization of the enzyme has been confirmed by electron microscopy in U-251 astrocytoma cells and by confocal laser microscopy in the same cells and in PC-12 cells, where the structurally similar isoform type V-sPLA 2 has mainly nuclear localization. In addition to sPLA 2 , mitochondria contain another phospholipase A 2 that is Ca 2؉ -independent and sensitive to bromoenol lactone, associated with the outer mitochondrial membrane. We hypothesize that, under reduced respiratory rate, brain mitochondria release sPLA 2 -IIA that might contribute to cell damage.

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Section: Discussionsupporting

confidence: 59%

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Macchioni¹,

Corazzi²,

Nardicchi³

et al. 2004

Journal of Biological Chemistry

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“…A high plasma level of sPLA 2 -IIA correlates positively with C-reactive protein (CRP) levels and predicts coronary events due to atherosclerosis. 28,30,61,63 This association is independent of other established risk factors. 28 Furthermore, positive correlations between sPLA 2 -IIA and soluble adhesion molecules, CRP, and antibody titers to oxidized LDL in plasma of hypercholesterolemic patients were recently reported.…”

mentioning

confidence: 69%

Phospholipase A ₂ in Vascular Disease

Hurt-Camejo

Camejo

Peilot

et al. 2001

Circulation Research

197

118

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Abstract-Secretory phospholipase A 2 (PLA 2 ) can be proatherogenic both in the circulation and in the arterial wall. In blood plasma, PLA 2 can modify the circulating lipoproteins and so induce formation of small dense LDL particles, which are associated with increased risk for cardiovascular disease. In the arterial wall, PLA 2 can hydrolyze lipoproteins. The PLA 2 -modified lipoproteins bind tightly to extracellular proteoglycans, which may lead to their enhanced retention in the arterial wall. The modified lipoproteins may also aggregate and fuse, which can lead to accumulation of their lipids within the extracellular matrix. The PLA 2 -modified particles are more susceptible to further modifications by other enzymes and agents and can be taken up by macrophages, leading to accumulation of intracellular lipids. In addition, lysophospholipids and free fatty acids, the hydrolysis products of PLA 2 , promote atherogenesis. Thus, these lipid mediators can be carried, either by the PLA 2 -modified lipoproteins themselves or by albumin, into the arterial cells, which then undergo functional alterations. This may, in turn, lead to specific changes in the extracellular matrix, which increase the retention and accumulation of lipoproteins within the matrix. In the present article, we discuss the possible actions of PLA 2 enzymes, especially PLA 2 -IIA, in the arterial wall during atherogenesis. (Circ Res. 2001;89:298-304.)

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“…Considering these findings, it is possible that PLA2-V may be present in human serum during bacteremia, and the bactericidal properties of acute phase serum may partly be explained by the presence of PLA2-V. However, PLA2-V has not been found in acute phase serum [23]. Therefore, it is most probable that PLA2-IIA is responsible for the bacterial killing in acute phase serum.…”

Section: Discussionmentioning

confidence: 97%

Bactericidal Group IIA Phospholipase A2 in Serum of Patients with Bacterial Infections

2002

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Group IIA phospholipase A2 (PLA2-IIA) is a newly recognized antibacterial acute phase protein. The concentration of PLA2-IIA increases up to 500-fold in the blood plasma of patients with severe acute diseases, compared with healthy persons. Despite numerous studies, the exact roles of this enzyme in human diseases are unknown. This study investigated the antibacterial properties of PLA2-IIA in human acute phase serum. PLA2-IIA in serum samples of patients with bacterial infections was capable of killing 90% of Staphylococcus aureus and 99% of Listeria monocytogenes in vitro after incubation for 2 h. At concentrations found in normal human serum, PLA2-IIA killed 90% of L. monocytogenes but did not kill S. aureus or Escherichia coli. The bactericidal effects of acute phase and normal human serum were abolished after depletion of PLA2-IIA by immunoadsorption.

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Sera of patients suffering from inflammatory diseases contain group IIA but not group V phospholipase A2

Cited by 18 publications

References 36 publications

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Phospholipase A ₂ in Vascular Disease

Bactericidal Group IIA Phospholipase A2 in Serum of Patients with Bacterial Infections

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Sera of patients suffering from inflammatory diseases contain group IIA but not group V phospholipase A2

Cited by 18 publications

References 36 publications

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Rat Brain Cortex Mitochondria Release Group II Secretory Phospholipase A2 under Reduced Membrane Potential

Phospholipase A 2 in Vascular Disease

Bactericidal Group IIA Phospholipase A2 in Serum of Patients with Bacterial Infections

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Product

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Phospholipase A ₂ in Vascular Disease