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Leukotriene B4 modulates P2X7 receptor-mediated Leishmania amazonensis elimination in murine macrophages.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 May 15; Vol. 192 (10), pp. 4765-73. Date of Electronic Publication: 2014 Apr 11. - Publication Year :
- 2014
-
Abstract
- ATP is an important signaling molecule in the immune system, and it is able to bind the P2X7 purinergic receptor. Recently, our group showed that ATP-treated macrophages eliminate Leishmania amazonensis. It has been reported that leukotriene B4 (LTB4) reduces the parasitic load of infected macrophages. Additionally, it has been demonstrated that the P2X7 receptor can induce PLA2 activation and arachidonic acid mobilization. Based on these findings, we investigated whether LTB4 is produced upon P2X7 receptor activation and examined whether LTB4 modulates parasite elimination. Using macrophages lacking the P2X7 receptor, we observed that ATP was not able to reduce L. amazonensis load. This result suggests a role of the P2X7 purinergic receptor in parasite elimination. In addition, ATP was sufficient to induce LTB4 release from infected control macrophages but not from macrophages lacking the P2X7 receptor. Moreover, we found that ATP failed to decrease the parasitic load in 5-lipoxygenase (LO)-deficient macrophages. Treatment with the 5-LO inhibitor AA861 also impairs the ATP effect on parasitic loads. Furthermore, macrophages from 5-LO knockout mice eliminated L. amazonensis in the presence of exogenous LTB4, and macrophages obtained from P2X7 receptor knockout mice eliminated L. amazonensis when incubated with ionomycin. Finally, we demonstrated that in the presence of CP105696, an antagonist for LTB4 high-affinity receptor, ATP was not able to reduce parasitic load. These results indicate that P2X7 receptor activation leads to LTB4 formation, which is required for L. amazonensis elimination.
- Subjects :
- Animals
Arachidonate 5-Lipoxygenase genetics
Arachidonate 5-Lipoxygenase immunology
Benzopyrans pharmacology
Benzoquinones pharmacology
Calcium Ionophores pharmacology
Carboxylic Acids pharmacology
Female
Ionomycin pharmacology
Leishmaniasis genetics
Leishmaniasis pathology
Leukotriene B4 genetics
Lipoxygenase Inhibitors pharmacology
Macrophages, Peritoneal parasitology
Macrophages, Peritoneal pathology
Mice
Mice, Inbred BALB C
Mice, Knockout
Receptors, Purinergic P2X7 genetics
Leishmania immunology
Leishmaniasis immunology
Leukotriene B4 immunology
Macrophages, Peritoneal immunology
Receptors, Purinergic P2X7 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 192
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24729618
- Full Text :
- https://doi.org/10.4049/jimmunol.1301058