Lipoxygenase-derived eicosanoids are involved in the inhibitory effect of Crotalus durissus terrificus venom or crotoxin on rat macrophage phagocytosis

Sampaio, Sandra Coccuzzo; Alba-Loureiro, Tatiana Carolina; Brigatte, Patrícia; Landgraf, Richardt Gama; Santos, E. C. dos; Curi, Rui; Cury, Yara

doi:10.1016/j.toxicon.2005.11.008

Cited by 47 publications

(39 citation statements)

References 52 publications

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“…The literature shows that group IIA sPLA 2 s interact with intracellular PLA 2 s in the biosynthesis of lipid mediators from fatty acids 6 and also that LD formation involves the activation of intracellular PLA 2 s, such as iPLA 2 and cPLA 2 , as well as other classes of intracellular phospholipases, including PLC and PLD 47–50 . Our finding that inhibition of iPLA 2 by BEL and FKGK11 reduced CB-induced LD biogenesis indicates that this intracellular PLA 2 contributes to the effect of CB.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to most group IIA sPLA 2 s, CB per se displays immunomodulatory effects 4, 5 . It is able to inhibit macrophage spreading and phagocytic activities, both of which are associated with increased levels of lipoxin A 4 (LXA 4 ), an important arachidonic acid-derived lipid mediator shown to be active in the resolution phase of inflammation 6 . CB also induces the biosynthesis and release of prostaglandin E 2 (PGE 2 ) and D 2 (PGD 2 ) via activation of the catalytic activity of cyclooxygenase-1 (COX-1) 7 .…”

Section: Introductionmentioning

confidence: 99%

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A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages

Giannotti

Leiguez

Carvalho

et al. 2017

Sci Rep

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Crotoxin B (CB) is a catalytically active group IIA sPLA2 from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA2s, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators. Here, the ability of CB to induce formation of LDs and the mechanisms involved in this effect were investigated in isolated macrophages. The profile of CB-induced 15-d-PGJ2 (15-Deoxy-Delta-12,14-prostaglandin J2) production and involvement of LDs in 15-d-PGJ2 biosynthesis were also investigated. Stimulation of murine macrophages with CB induced increased number of LDs and release of 15-d-PGJ2. LDs induced by CB were associated to PLIN2 recruitment and expression and required activation of PKC, PI3K, MEK1/2, JNK, iPLA2 and PLD. Both 15-d-PGJ2 and COX-1 were found in CB-induced LDs indicating that LDs contribute to the inhibitory effects of CB by acting as platform for synthesis of 15-d-PGJ2, a pro-resolving lipid mediator. Together, our data indicate that an immunomodulatory GIIA sPLA2 can directly induce LD formation and production of a pro-resolving mediator in an inflammatory cell and afford new insights into the roles of LDs in resolution of inflammatory processes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages

Giannotti

Leiguez

Carvalho

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Desenvolve-se facilmente em regiões distintas, tais como cérebro (Morioka et al, 1992), tecido subcutâneo (Bacurau et al, 2000;Belo et al, 2010;Maria et al, 1994;Veiga et al, 2008), tecido muscular (Soares et al, 1994), cavidade peritoneal (Rosa et al, 1993 A concentração da crotoxina foi determinada a partir de dados da literatura indicando que esta corresponde a 60% do veneno bruto (Slotta, Fraenkel-Conrat, 1938) e baseada em estudos anteriores (Sampaio et al, 2006(Sampaio et al, , 2007.…”

Section: Modelos Experimentais Para O Estudo De Neoplasias -Tumores Sunclassified

Efeito da crotoxina sobre função e o metabolismo de glicose e glutamina de macrófagos durante a progressão tumoral.

Faiad¹

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“…Estes efeitos são modulados, pelo menos em parte, por mediadores gerados na via da lipoxigenase (SAMPAIO et al, 2006a Apesar das evidências da ação antitumoral da CTX, e de que esta toxina acarreta inibição tanto na fosforilação de tirosina quinase quanto na expressão das proteínas Rho GTPases, efeito mediado por derivados da via 5-lipoxigenase, não foi demostrado, até o momento, a ação desta toxina sobre a angiogênese. Estudos demonstrando a ação da CTX sobre parâmetros fundamentais para a neovascularização pode contribuir para novas perspectivas no desenvolvimento de uma nova substância com propriedades terapêuticas no controle de neoplasias.…”

Section: Crotoxinaunclassified

Caracterização da ação inibitória da crotoxina sobre as funções de células endoteliais em matriz extracelular bidimensional e tridimensional. Estudos in vitro.

Kato¹

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Lipoxygenase-derived eicosanoids are involved in the inhibitory effect of Crotalus durissus terrificus venom or crotoxin on rat macrophage phagocytosis

Cited by 47 publications

References 52 publications

A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages

A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages

Efeito da crotoxina sobre função e o metabolismo de glicose e glutamina de macrófagos durante a progressão tumoral.

Caracterização da ação inibitória da crotoxina sobre as funções de células endoteliais em matriz extracelular bidimensional e tridimensional. Estudos in vitro.

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