Browsing by Subject "Phospholipase A2"

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    Characterizing Phospholipase A2-Induced Spinal Cord Injury—A Comparison with Contusive Spinal Cord Injury in Adult Rats
    (Springer, 2011) Liu, Nai-Kui; Titsworth, William Lee; Zhang, Yi Ping; Xhafa, Aurela I.; Shields, Christopher B.; Xu, Xiao-Ming; Neurological Surgery, School of Medicine
    To assess whether phospholipase A2 (PLA2) plays a role in the pathogenesis of spinal cord injury (SCI), we compared lesions either induced by PLA2 alone or by a contusive SCI. At 24-h post-injury, both methods induced a focal hemorrhagic pathology. The PLA2 injury was mainly confined within the ventrolateral white matter, whereas the contusion injury widely affected both the gray and white matter. A prominent difference between the two models was that PLA2 induced a massive demyelination with axons remaining in the lesion area, whereas the contusion injury induced axonal damage and myelin breakdown. At 4 weeks, no cavitation was found within the PLA2 lesion, and numerous axons were myelinated by host-migrated Schwann cells. Among them, 45% of animals had early transcranial magnetic motor-evoked potential (tcMMEP) responses. In contrast, the contusive SCI induced a typical centralized cavity with reactive astrocytes forming a glial border. Only 15% of rats had early tcMMEP responses after the contusion. BBB scores were similarly reduced in both models. Our study indicates that PLA2 may play a unique role in mediating secondary SCI likely by targeting glial cells, particularly those of oligodendrocytes. This lesion model could also be used for studying demyelination and remyelination in the injured spinal cord associated with PLA2-mediated secondary SCI.
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    Cytosolic phospholipase A2 expression patterns in brain following the traumatic brain injury
    (2010-06-01T16:58:17Z) Yang, Shuangni; Cummins, Theodore R.; Chen, Jinhui; Xu, Xiaoming
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    Polarization of Macrophages toward M2 Phenotype Is Favored by Reduction in iPLA2β (Group VIA Phospholipase A2)
    (American Society for Biochemistry and Molecular Biology, 2016-10-28) Ashley, Jason W.; Hancock, William D.; Nelson, Alexander J.; Bone, Robert N.; Tse, Hubert M.; Wohltmann, Mary; Turk, John; Ramanadham, Sasanka; Medicine, School of Medicine
    Macrophages are important in innate and adaptive immunity. Macrophage participation in inflammation or tissue repair is directed by various extracellular signals and mediated by multiple intracellular pathways. Activation of group VIA phospholipase A2 (iPLA2β) causes accumulation of arachidonic acid, lysophospholipids, and eicosanoids that can promote inflammation and pathologic states. We examined the role of iPLA2β in peritoneal macrophage immune function by comparing wild type (WT) and iPLA2β−/− mouse macrophages. Compared with WT, iPLA2β−/− macrophages exhibited reduced proinflammatory M1 markers when classically activated. In contrast, anti-inflammatory M2 markers were elevated under naïve conditions and induced to higher levels by alternative activation in iPLA2β−/− macrophages compared with WT. Induction of eicosanoid (12-lipoxygenase (12-LO) and cyclooxygenase 2 (COX2))- and reactive oxygen species (NADPH oxidase 4 (NOX4))-generating enzymes by classical activation pathways was also blunted in iPLA2β−/− macrophages compared with WT. The effects of inhibitors of iPLA2β, COX2, or 12-LO to reduce M1 polarization were greater than those to enhance M2 polarization. Certain lipids (lysophosphatidylcholine, lysophosphatidic acid, and prostaglandin E2) recapitulated M1 phenotype in iPLA2β−/− macrophages, but none tested promoted M2 phenotype. These findings suggest that (a) lipids generated by iPLA2β and subsequently oxidized by cyclooxygenase and 12-LO favor macrophage inflammatory M1 polarization, and (b) the absence of iPLA2β promotes macrophage M2 polarization. Reducing macrophage iPLA2β activity and thereby attenuating macrophage M1 polarization might cause a shift from an inflammatory to a recovery/repair milieu.