Phospholipase A2 enzymes: regulation and inhibition

Glaser, Keith B.; Mobilio, Dominick; Chang, Joseph; Senko, Nancy

doi:10.1016/0165-6147(93)90071-q

Cited by 243 publications

(117 citation statements)

References 40 publications

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“…A severe reduction in fMLP-stimulated O 2 -. release was also exhibited by MP, a sPLA 2 inhibitor (Glaser et al, 1993). In conclusion, we suggest that the last enzyme (sPLA 2 ) is involved in oxygen free radical production.…”

Section: Discussionmentioning

confidence: 79%

“…It is generally accepted that among the enzymes determining the rate-limiting step in eicosanoid and PAF formation, phospholipases A 2 (PLA 2 s EC 3.1.1.4. phosphatide sn-2 acylhydrolase) play a role (Glaser et al, 1993). 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).…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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Section: Discussionmentioning

confidence: 79%

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

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“…4) [123]. Mammalian leukocytes contain several types of PLA 2 enzymes, the type most commonly involved in arachidonic acid production being high-molecular-mass (85 kDa) cytosolic PLA 2 (cPLA 2 ) [10,11] which requires micromolar concentrations of Ca 2+ for translocation from the cytosol to the nuclear envelope [44,45,47,63,123]. The cPLA 2 activity seems to be regulated by G proteins and by protein kinase C [79,90].…”

Section: Death Pathwaysmentioning

confidence: 99%

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

2005

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-Mannheimia haemolytica induced pneumonias are only observed in goats, sheep and cattle. The bacterium produces several virulence factors,whose principal ones are lipopolysaccharide and leukotoxin. The latter is cytotoxic only for ruminant leukocytes, a phenomenon that is correlated with its ability to bind and interact with the ruminant β2-integrin Lymphocyte Function-associated Antigen 1. This paper globally reviews all the information available on host-pathogen interactions underlying respiratory mannheimiosis (formerly pasteurellosis), from the stable and the Petri dish to the biochemical cascade of events triggered by the leukotoxin inside ruminant leukocytes. One conclusion can be made: the most widespread cattle respiratory disease with the most important impact on beef production worldwide, is probably due to a tiny ruminant-specific focal variation in the CD18-and/or CD11a-expressing genes.

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“…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

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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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Phospholipase A2 enzymes: regulation and inhibition

Cited by 243 publications

References 40 publications

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

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

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

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

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Phospholipase A2 enzymes: regulation and inhibition

Cited by 243 publications

References 40 publications

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

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

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

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

Contact Info

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

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

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