Effects of leukotriene C4 on macrophage association with and intracellular fate of Trypanosoma cruzi

139

131

Section: Equivalent Cellular Infiltration In the Liver Of Wt And Il-1mentioning

confidence: 99%

IL-17 Is Necessary for Host Protection against Acute-Phase Trypanosoma cruzi Infection

Miyazaki

Hamano

Wang

et al. 2010

139

131

“…Wirth et al (11,12) reported that both LTB 4 and LTC 4 increased the phagocytosis and killing of Trypanosoma cruzi by peritoneal macrophages. The IFN-␥-mediated killing of Toxoplasma gondii by human monocytes was shown to be dependent on LT biosynthesis (13).…”

mentioning

confidence: 99%

Leukotrienes Are Essential for the Control ofLeishmania amazonensisInfection and Contribute to Strain Variation in Susceptibility

Serezani

Perrela

Russo

et al. 2006

Leukotrienes (LTs) are known to be produced by macrophages when challenged with Leishmania, but it is not known whether these lipid mediators play a role in host defense against this important protozoan parasite. In this study, we investigated the involvement of LTs in the in vitro and in vivo response to Leishmania amazonensis infection in susceptible (BALB/c) and resistant (C3H/HePAS) mice. Pharmacologic or genetic deficiency of LTs resulted in impaired leishmanicidal activity of peritoneal macrophages in vitro. In contrast, addition of LTB4 increased leishmanicidal activity and this effect was dependent on the BLT1 receptor. LTB4 augmented NO production in response to L. amazonensis challenge, and studies with a NO synthesis inhibitor revealed that NO was critical for the enhancement of macrophage leishmanicidal activity. Interestingly, macrophages from resistant mice produced higher levels of LTB4 upon L. amazonensis challenge than did those from susceptible mice. In vivo infection severity, as assessed by footpad swelling following s.c. promastigote inoculation, was increased when endogenous LT synthesis was abrogated either pharmacologically or genetically. Taken together, these results for the first time reveal an important role for LTB4 in the protective response to L. amazonensis, identify relevant leishmanicidal mechanisms, and suggest that genetic variation in LTB4 synthesis might influence resistance and susceptibility patterns to infection.

“…In addition to their demonstrated pro and antiinflammatory properties, phagocyte-derived eicosanoids have been implicated in the control of infections. In in vitro and in vivo models, the eicosanoids have been shown to modulate the microbicidal activity of phagocytes (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

Requirement of JNK-Mediated Phosphorylation for Translocation of Group IVA Phospholipase A2 to Phagosomes in Human Macrophages

Casas

Meana²,

Esquinas³

et al. 2009

Eicosanoids are a broad family of lipids that play a critical role in host defense against bacterial and fungal infections. The first enzyme in the metabolic pathway for the generation of eicosanoids is group IVA phospholipase A2, also known as cytosolic phospholipase A2α (cPLA2α). During phagocytosis, cPLA2α has been found to translocate to the phagosome, although the molecular mechanism involved in such a translocation has not been elucidated. By using enhanced GFP-tagged proteins we show in this work that a nonphosphorylatable cPLA2α mutant (S505A) does not translocate to the phagosomes, but a mutant that mimics phosphorylation on Ser505 (S505E) does it so readily. During phagocytosis, endogenous cPLA2α is phosphorylated at Ser505, and inhibitors of JNK, but not of other related kinases such as p38 or the extracellular-regulated kinases 1 and 2, completely block such a phosphorylation. Inhibition of JNK activity also inhibits the translocation of cPLA2α to phagosomal membranes, as well as arachidonic acid release to the extracellular medium. Moreover, the S505E mutant makes the enzyme refractory to JNK inhibition, translocating normally to phagosomal membranes. Collectively, these data support a key role for JNK-mediated cPLA2α phosphorylation at Ser505 in the sequence of events leading to translocation and activation of the enzyme to phagosomal membranes in human macrophages.