Phospholipase A2 enzymes: Regulation and physiological role

Mukherjee, Anil B.; Miele, Lucio; Pattabiraman, Nagarajan

doi:10.1016/0006-2952(94)90216-x

Cited by 196 publications

(183 citation statements)

References 64 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…In activated neutrophils, activation of various phospholipases (PLA) (35) leads to increased intracellular levels of free arachidonate, some of which is used for leukotriene biosynthesis and some of which is released into the extracellular medium (3,36,37). However, the sources of arachidonate released into the medium as well as the lipase(s) involved in this process are still a matter of controversy.…”

Section: Discussionmentioning

confidence: 99%

Protein-facilitated Export of Arachidonic Acid from Pig Neutrophils

Krischer¹,

Eisenmann²,

Böck³

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

Activated neutrophils release a variety of eicosanoids into the extracellular medium including arachidonic acid, 5-hydroxyicosatetraenoic acid, and leukotriene A 4 and B 4 . In this study, the mechanism of arachidonic acid export has been examined using inside-out plasma membrane vesicles from pig polymorphonuclear leukocytes. Tritiated arachidonic acid associated rapidly with the membrane vesicles and crossed the membrane into the intravesicular space in a time-dependent and saturable manner. Half the maximal influx rate was measured at an arachidonate concentration of 5.7 M, and a maximal influx velocity of 3.0 nmol/mg ؋ min was determined at pH 6.8. Influx into vesicles was sensitive to a number of common anion transport inhibitors including pentachlorophenol, phloretin, diiodosalicylic acid, and quercetin as well as to the proteases trypsin and Pronase, suggesting a protein-dependent process. Furthermore, influx was temperature-sensitive with an energy of activation of 11.6 kcal/mol. Varying extravesicular concentration of ATP, Na ؉ , or K ؉ had no impact on arachidonate influx, whereas changes in pH had a profound effect; optimum transport activity was observed at an extravesicular pH of 6, whereas raising the pH to 9.5 essentially abolished uptake. These results indicate and initially characterize a novel protein-facilitated arachidonate export mechanism in pig neutrophils.

show abstract

Section: Discussionmentioning

confidence: 99%

Protein-facilitated Export of Arachidonic Acid from Pig Neutrophils

Krischer¹,

Eisenmann²,

Böck³

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…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). 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).…”

Section: Discussionmentioning

confidence: 99%

“…Secretory PLA2s have a molecular mass of about 14 kDa and can be divided into groups I (mammalian pancreas, Elapidae and Hydrophidae snake venoms) and II (Crotalidae and Viperidae snake venoms, as well as in mammalian platelets, neutrophils, peritoneum, synovial fluids...). Other low molecular weight PLA2s can be found in the venoms of bees and wasps and are included in a different group (III), for they are not closely related to the enzymes in groups I and II (Glaser et al, 1993;Mukherjee et al, 1994). High molecular weight PLA2s (about 85 kDa) are present in various mammalian cells such as platelets, macrophage cell lines and neutrophils (Clarke et al, 1990;Takayama et al, 1991;Ramesha & Ives, 1993).…”

Section: Introductionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…PLA 2 s, enzymes which are able to hydrolyze the sn-2-ester bond in phospholipids, exist in distinct forms with di erent molecular mass, substrate speci®city, structure and catalytic mechanism (Mukherjee et al, 1994). Among these, the 85 kDa cytosolic PLA 2 (cPLA 2 ) has been shown to prefer the arachidonic acid in sn-2-position, thus suggesting that this enzyme is responsible for arachidonic acid release and cascade.…”

Section: Introductionmentioning

confidence: 99%

Influence of interleukin 1α on superoxide anion, platelet activating factor release and phospholipase A₂ activity of naive and sensitized guinea‐pig alveolar macrophages

Mugnai¹,

Ciuffi²,

Maurizi³

et al. 1997

British J Pharmacology

View full text Add to dashboard Cite

1 We studied the e ect exerted by hr-interleukin-1a (IL-1a) on responsiveness of alveolar macrophages (AM) from naive and sensitized guinea-pigs, through O 2 -. production (by ferricytochrome C reduction), platelet-activating factor (PAF) release (by platelet aggregation), prostaglandin E 2 (PGE 2 ) release (by a radioimmunoassay), and cytosolic phospholipase A 2 (cPLA 2 ) activity (by hydrolysis of radioactive substrate). 2 In naive guinea-pig AM, 0.06 nM hr-IL-1a pretreatment decreased by 65% O 2 -. release stimulated with 10 nM fMLP. In contrast, O 2 -. production was not a ected in sensitized guinea-pig AM.3 O 2 -. release elicited by fMLP stimulation in both cell groups was a ected by PLA 2 inhibitors (10 mM bromophenacyl bromide, BPB or 10 mM methylprednisolone, MP). In contrast, 10 mM arachidonyl tri¯uoromethyl ketone (AACOCF 3 ), a cPLA 2 inhibitor, was ine ective. 4 In naive AM, PAF release was elicited by hr-IL-1a pretreatment and by separate fMLP-stimulation, but when the stimulus was added to hr-IL-1a-pretreated cells inhibition of PAF release was observed. In sensitized AM, PAF release was lower than that found in naive guinea-pig AM in both hr-IL-1a-pretreated and fMLP-stimulated cells. 5 PGE 2 release was una ected by hr-IL-1a pretreatment and it was decreased by fMLP in both naive and sensitized AMs. The latter released less PGE 2 than naive cells in basal conditions and after fMLP treatment. 6 Sensitized AM showed a greater cPLA 2 activity in all experimental conditions in comparison to naive cells. cPLA 2 activity assayed in the cytosolic fraction was found to be enhanced by hr-IL-1a pretreatment and by fMLP stimulation in naive but not in sensitized AM. However, when the stimulus was added to hr-IL-1a-pretreated cells we observed a decrease in cPLA 2 activity in the cytosol and an increase in the membranes, thus suggesting a translocation of enzymatic activity. 7 In conclusion, hr-IL-1a can modulate the responsiveness of AM from naive and sensitized guineapigs, as suggested by changes found in the release of PAF and O 2 -. and in cPLA 2 activity; therefore, sensitization itself may a ect cellular responsiveness.

show abstract

Phospholipase A2 enzymes: Regulation and physiological role

Cited by 196 publications

References 64 publications

Protein-facilitated Export of Arachidonic Acid from Pig Neutrophils

Protein-facilitated Export of Arachidonic Acid from Pig Neutrophils

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

Influence of interleukin 1α on superoxide anion, platelet activating factor release and phospholipase A₂ activity of naive and sensitized guinea‐pig alveolar macrophages

Contact Info

Product

Resources

About

Phospholipase A2 enzymes: Regulation and physiological role

Cited by 196 publications

References 64 publications

Protein-facilitated Export of Arachidonic Acid from Pig Neutrophils

Protein-facilitated Export of Arachidonic Acid from Pig Neutrophils

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

Influence of interleukin 1α on superoxide anion, platelet activating factor release and phospholipase A2 activity of naive and sensitized guinea‐pig alveolar macrophages

Contact Info

Product

Resources

About

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

Influence of interleukin 1α on superoxide anion, platelet activating factor release and phospholipase A₂ activity of naive and sensitized guinea‐pig alveolar macrophages