Structure and Properties of a Secretable Phospholipase A2 from Human Platelets

Kramer, Ruth M.; Johansen, Berit; Hession, Catherine; Pepinsky, R. Blake

doi:10.1007/978-1-4684-5805-3_3

Cited by 109 publications

(129 citation statements)

References 66 publications

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“…In addition, snpPLA 2 is a very basic protein (pI, 10.5) containing 23 arginine and lysine residues but only 8 glutamic and aspartic acid residues. 50 One consequence of its net positive charges is that snpPLA 2 binds to sulfated GAGs. 33,51 For its activity, snpPLA 2 requires millimolar concentrations of calcium.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural Localization of Secretory Type II Phospholipase A ₂ in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

Romano¹,

Romano²,

Björkerud³

et al. 1998

ATVB

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Abstract-We recently reported on the immunolocalization of type II secretory nonpancreatic phospholipase A 2 (snpPLA 2 ) in human atherosclerotic lesions. In the present study, we present data on the distribution and ultrastructural localization of snpPLA 2 in adjacent nonatherosclerotic and atherosclerotic regions of human arteries. Electron microscopy (EM) of immunogold labeling techniques with a monoclonal antibody was used to analyze arterial tissue. The human specimens analyzed were obtained from autopsy and surgery cases. The results with EM showed a stronger snpPLA 2 immunoreactivity in regions of arteries with atherosclerotic lesions than in regions without lesions from the same individual. snpPLA 2 immunoreactivity was stronger in the arterial intima of atherosclerotic than of nonatherosclerotic tissue. EM-immunogold examination revealed that the majority of snpPLA 2 was localized along the extracellular matrix, associated with collagen fibers and other extracellular matrix structures. Intracellular snpPLA 2 was observed in electron-dense vesicles in intimal cells. snpPLA 2 was also found in contact with large, extracellular lipid droplets. These results support the hypothesis that extracellular snpPLA 2 is localized at sites where it may hydrolyze phospholipids from lipoproteins and lipid aggregates retained in the extracellular matrix of the arterial wall. This may be a mechanism for in situ release of proinflammatory lipids, free fatty acids, and lysophosphatidylcholine in regions of apolipoprotein B accumulation, which are abundant in atherosclerotic lesions. (Arterioscler Thromb Vasc Biol. 1998;18:519-525.)

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Section: Discussionmentioning

confidence: 99%

Ultrastructural Localization of Secretory Type II Phospholipase A ₂ in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

Romano¹,

Romano²,

Björkerud³

et al. 1998

ATVB

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“…Cyto- solic and secretory PLA2s have been described in a number of cells, including neutrophils (Traynor & Authi, 1981;Balsinde et al, 1988;Ramesha & Ives, 1993), monocytes (Wightman et al, 1981;Ulevitch et al, 1988;Clark et al, 1990) and platelets (Matsumoto et al, 1988;Kramer et al, 1989;Takayama et al, 1991). PLA2 enzymes may be involved in cell proliferation and signal transduction as well as in the pathogenesis of disease processes such as inflammation (Mukherjee et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…PLA2 enzymes may be involved in cell proliferation and signal transduction as well as in the pathogenesis of disease processes such as inflammation (Mukherjee et al, 1994). Secretory PLA2s with the biochemical properties of group II enzymes can be induced and secreted from cytokine-stimulated cells (Daniels et al, 1992;Glaser et al, 1993;Angel et al, 1993), and they are present at high levels in synovial fluid, peripheral blood, neutrophils and monocytes of patients with rheumatoid arthritis (Kramer et al, 1989;Bomalaski & Clark, 1993). In this experimental model the synthesis and secretion of PLA2 can be induced by TNFa, for this cytokine enhances the expression of group II PLA2 and may also facilitate membrane phospholipid hydrolysis by this enzyme (Kudo et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Involvement of secretory phospholipase A₂ activity in the zymosan rat air pouch model of inflammation

Payá

Terencio

Ferrándiz

et al. 1996

British J Pharmacology

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1 In the zymosan rat air pouch model of inflammation we have assessed the time dependence of phospholipase A2 (PLA2) accumulation in the inflammatory exudates as well as cell migration, myeloperoxidase activity, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. 2 A significant increase in PLA2 activity was detected in 1,200 g supernatants of exudates 8 h after injection of zymosan into rat air pouch. This event coincided with peaks in cell accumulation (mainly neutrophils) and myeloperoxidase activity in exudates and was preceded by a rise in eicosanoid levels. 3 This enzyme (without further purification) behaved as a secretory type II PLA2 with an optimum pH at 7-8 units, lack of selectivity for arachidonate release and dependence on mM calcium concentrations for maximal activity. 4 The PLA2 inhibitors manoalide and scalaradial inhibited this enzyme activity in vitro in a concentration-dependent manner. Scalaradial also inhibited zymosan stimulated myeloperoxidase release in vitro.5 Injection of the marine PLA2 inhibitor scalaradial together with zymosan into the pouch at doses of 0.5, 1 and 5 umol per pouch resulted in a dose-dependent inhibition of PLA2 activity in exudates collected 8 h later. Myeloperoxidase levels and cell migration were also decreased, while eicosanoid levels were not modified. 6 Colchicine administration to rats prevented infiltration and decreased PLA2 levels in the 8 h zymosan-injected air pouch. 7 These results indicate that during inflammatory response to zymosan in the rat air pouch a secretory PLA2 activity is released into the exudates. The source of this activity is mainly the neutrophil which migrates into the pouch. 8 Scalaradial exerts anti-inflammatory effects in the zymosan air pouch.

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“…PLA2 plays an important role in inflammation by releasing arachidonic acid from membrane phospholipids for eicosanoid synthesis (van den Bosch 1980). Several human PLA2 genes have been cloned: pancreatic group I PLA2 (Seilhamer et al 1986), synovial-type group II PLA2 (Kramer et al 1989;Seilhamer et al 1989), cytosolic PLA2 (Clark et al 1991), and a 12-cysteine PLA2 distinct from group I PLA2 and group II PLA2 (Chen et al 1994). In addition, a number of other PLA2s have been purified from mammalian tissues (Dennis 1994).…”

mentioning

confidence: 99%

Expression of Human Group II Phospholipase A₂in Transgenic Mice

Nevalainen

Laine

Grass

1997

J Histochem Cytochem.

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SUMMARY Group II phospholipase A 2 (PLA2) has been proposed to play an important role in inflammation and defense against bacterial infection. We investigated tissues of transgenic mice expressing the human group II PLA2 gene by immunohistochemistry using rabbit anti-human group II PLA2 antibodies, and by in situ hybridization by probing with human group II PLA2 mRNA anti-sense (test) and sense (control) riboprobes. By immunohistochemistry, human group lI PLA2 was found in various mouse tissues and cell types including hepatocytes, proximal tubule cells of the kidney, epithelial cells of the renal pelvis, urinary bladder and ureter, granulosa cells of Graafian follicles, aortic intima and media, cartilage, epiphyseal bone, bronchial epithelial cells, and connective tissue cells in the dermis. By in situ hybridization, group ll PLA2 mRNA was localized in hepatocytes, epidermal cells, dermal cells, connective tissue fibroblasts, epithelial and smooth muscle cells of the urinary bladder, and cells of Bowman's capsule. These results show that human group ll PLA2 is expressed in large amounts in hepatocytes and many extrahepatic tissues of the transgenic mice. These animals provide a useful new tool for studies on the metabolism, in vivo effects, and physiological and pathological roles of phospholipase A 2 .

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Structure and Properties of a Secretable Phospholipase A2 from Human Platelets

Cited by 109 publications

References 66 publications

Ultrastructural Localization of Secretory Type II Phospholipase A ₂ in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

Ultrastructural Localization of Secretory Type II Phospholipase A ₂ in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

Involvement of secretory phospholipase A₂ activity in the zymosan rat air pouch model of inflammation

Expression of Human Group II Phospholipase A₂in Transgenic Mice

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Structure and Properties of a Secretable Phospholipase A2 from Human Platelets

Cited by 109 publications

References 66 publications

Ultrastructural Localization of Secretory Type II Phospholipase A 2 in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

Ultrastructural Localization of Secretory Type II Phospholipase A 2 in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

Involvement of secretory phospholipase A2 activity in the zymosan rat air pouch model of inflammation

Expression of Human Group II Phospholipase A2in Transgenic Mice

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Resources

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Ultrastructural Localization of Secretory Type II Phospholipase A ₂ in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

Ultrastructural Localization of Secretory Type II Phospholipase A ₂ in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

Involvement of secretory phospholipase A₂ activity in the zymosan rat air pouch model of inflammation

Expression of Human Group II Phospholipase A₂in Transgenic Mice