Platelet activating factor receptor-deficient mice present delayed interferon-γ upregulation and high susceptibility to Leishmania amazonensis infection

Santiago, Helton da Costa; Pires, Maíra Faria Braga; Souza, Daniele G.; Roffê, Ester; Côrtes, Denise Fonseca; Tafuri, Wagner Luiz; Teixeira, Mauro M.; Vieira, Leda Quércia

doi:10.1016/j.micinf.2006.06.011

Cited by 30 publications

(31 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, no increased expression of arginase was found when footpad lesions from mice infected with L. amazonensis or L. major was compared. On the contrary, both NO synthase and arginase were upregulated in footpads of mice infected with L. major compared to those infected with L. amazonensis (Santiago et al 2006). In fact, the potential for NO and arginase production by macrophages harvested from infected mice at the time points prior to and during the divergence of lesion sizes, which were determined in vitro, were quite similar.…”

Section: Discussionmentioning

confidence: 88%

See 1 more Smart Citation

Low and high-dose intradermal infection with Leishmania majorand Leishmania amazonensis in C57BL/6 mice

Côrtes

Carneiro

Santos

et al. 2010

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 88%

“…A technical problem yet to be identified prevented us from obtaining good mRNA extractions and reverse-translations. As we have successfully resolved cytokines and chemokines in footpads previously (Santiago et al 2004(Santiago et al , 2006, the reason for our problem is likely related to the ear tissue.…”

Section: Discussionmentioning

confidence: 95%

Low and high-dose intradermal infection with Leishmania majorand Leishmania amazonensis in C57BL/6 mice

Côrtes

Carneiro

Santos

et al. 2010

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

“…Accordingly, PAF receptor (PAF receptor) is perhaps the most feasible candidate to serve as an HPC receptor. Indeed, PAF receptor-deficient mice were more susceptible to L. amazonensis infection and showed a delayed IFN-g production and higher arginase activity, suggesting an essential role for PAF receptor signaling in the control of L. amazonensis infection in mice (16). Thus, consistent with its structural similarities to PAF, our hypothesis was that HPC had at least partial requirement for PAF receptor to exert its leishmanicidal function through immunomodulation of macrophages, the obligate host cell for Leishmania.…”

mentioning

confidence: 52%

“…Mice were treated with miltefosine (20 mg/kg body weight) for 7 d consecutively by gavage 2 wk after L. donovani infection. Parasite burden in mice was assessed by limiting dilution and expressed as the negative log of the titer (16). Experimental protocols were approved by the ethical committee CETEA/UFMG protocol 150/09.…”

Section: Methodsmentioning

confidence: 99%

Platelet-Activating Factor Receptor Contributes to Antileishmanial Function of Miltefosine

Gangalum

Castro

Vieira

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Miltefosine [hexadecylphosphocholine (HPC)] is the only orally bioavailable drug for the disease visceral leishmaniasis, which is caused by the protozoan parasite Leishmania donovani. Although miltefosine has direct leishmanicidal effects, evidence is mounting for its immune system–dependent effects. The mechanism of such indirect antileishmanial effects of miltefosine remains to be discovered. As platelet-activating factor and HPC share structural semblances and both induce killing of intracellular Leishmania, we surmised that platelet-activating factor (PAF) receptor had a significant role in the antileishmanial function of miltefosine. The proposition was supported by molecular dynamic simulation of HPC docking into PAF receptor and by comparison of its leishmanicidal function on PAF receptor–deficient macrophages and mice under HPC treatment. We observed that compared with wild-type macrophages, the PAF receptor–deficient macrophages showed 1) reduced binding of a fluorescent analog of HPC, 2) decreased TNF-α production, and 3) lower miltefosine-induced killing of L. donovani. Miltefosine exhibited significantly compromised leishmanicidal function in PAF receptor–deficient mice. An anti-PAF receptor Ab led to a significant decrease in miltefosine-induced intracellular Leishmania killing and IFN-γ production in a macrophage–T cell coculture system. These results indicate significant roles for PAF receptor in the leishmanicidal activity of HPC. The findings open new avenues for a more rational understanding of the mechanism of action of this drug as well as for improved therapeutic strategies.

show abstract

“…PAF is also implicated in leishmaniasis, while several molecules with inhibitory effect towards PAF seem also to act beneficially in both Leishmania and HIV infections (4,(12)(13)(14)(15)(16). However, the demonstration that PAF and its basic biosynthetic enzymes can derive also from the Leishmania parasites is a novel and previously undescribed finding.…”

mentioning

confidence: 99%

Paf-Metabolic Enzymes and Paf-like Activity inL. InfantumandL. MajorPromastigotes

et al. 2011

View full text Add to dashboard Cite

Leishmania spp are obligate intracellular protozoan parasites of the mononuclear phagocyte system that cause a spectrum of diseases known as leishmaniasis. Platelet Activating Factor (PAF) and some PAF-antagonists seem to play a key role in Leishmania infection. In this article we detected for the first time the specific activities of PAF basic metabolic enzymes, PAF cholinephosphotransferase (PAF-CPT) and Lyso-PAF-acetylotransferase (Lyso-PAF-AT), in two species of Leishmania, namely Leishmania major (L. major) and Leishmania infantum (L. infantum). Specific activity of PAF-CPT of L. major homogenates was substantially higher than that of L. infantum homogenates, while Lyso-PAF-AT specific activities of the homogenates of both species were detected in the same levels. In addition, PAF-like molecules were detected in cells and their culture medium of both species. These results show that PAF-biosynthesis exists and varies between Leishmania species, findings that are in correlation with the general idea that the presence of PAF in several Leishmania species is implicated in Leishmania infection.

show abstract

Platelet activating factor receptor-deficient mice present delayed interferon-γ upregulation and high susceptibility to Leishmania amazonensis infection

Cited by 30 publications

References 30 publications

Low and high-dose intradermal infection with Leishmania majorand Leishmania amazonensis in C57BL/6 mice

Low and high-dose intradermal infection with Leishmania majorand Leishmania amazonensis in C57BL/6 mice

Platelet-Activating Factor Receptor Contributes to Antileishmanial Function of Miltefosine

Paf-Metabolic Enzymes and Paf-like Activity inL. InfantumandL. MajorPromastigotes

Contact Info

Product

Resources

About