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

Abstract

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.

Lysophosphatidic acid inhibition of the accumulation of Pseudomonas aeruginosa PAO1 alginate, pyoverdin, elastase and LasA

“…Evidence also exists suggesting that limiting phosphate availability may also be an environmental signal in inducing phospholipase C synthesis (Shortridge et al, 1992). In the present study, evidence is presented which indicates that a specific lysophospholipid, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphate [also called monopalmitoylphosphatidic acid (MPPA)], which is generated by the secretory phospholipase A2 and accumulates in inflammatory exudates (Fourcade et al, 1998 ;Paya et al, 1996), inhibits the extracellular accumulation of alginate, pyoverdin, elastase and LasA protease in cultures of P. aeruginosa PAO1 grown in Luria broth (LB).…”

“…MPPA is a member of a class of phospholipids called lysophosphatidic acids, which contain one fatty acid esterified to the C1 atom of the glycerol moiety, but which are lacking the fatty acid normally esterified to the C2 atom of the glycerol moiety. Lysophosphatidic acids are believed to be generated from the phosphatidic acid present in the inner leaflet of damaged cell membranes (Fourcade et al, 1998) by secretory phospholipase A2, which accumulates in inflammatory exudates (Paya et al, 1996). Lysophosphatidic acids have recently been implicated in blocking neutrophil recruitment to damaged lung tissue (Abraham et al, 1995) and in inhibiting the metabolic burst of human neutrophils (Chettibi et al, 1994).…”

Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity

“…The sPLA2 activity in BALF as well as supernatants of expectorations was measured using 3 H-OA-labelled E. coli membrane phospholipids as substrate 67,68 . In brief, aliquots of BALFs or supernatants of expectorations (1-10 ml) were incubated with 10 ml substrate (containing around 6,000 c.p.m.)…”

Modulatory Effect of Bolinaquinone, a Marine Sesquiterpenoid, on Acute and Chronic Inflammatory Processes

“…We tested the effect of this marine compound on an animal model in which high levels of secretory type II sPLA 2 is generated (Payá et al, 1996). As shown in Fig.…”