Modulation ofLeishmania (L.) amazonensisGrowth in Cultured Mouse Macrophages by Prostaglandins and Platelet Activating Factor (original) (raw)
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Mediators of Inflammation, 1994
Ttm role of endogenously synthesized PAF and prostaglandins on the infection of mouse macrophages by Letsbmanta (L) amazonensis was investigated, as well as the possible correlation between the effects of these inflammatory mediators with nitric oxide production. It was found that pretreatment of macrophages with 10-M of the PAF antagonists, BN-52021 or WEB-2086, increased macrophage infection by 17 and 59%, respectively. The cyclooxygenase inhibitor, indomethacin (10 g/ml), induced a significant inhibition which was reversed by addition of PGE (10 -3 M) to the culture medium. These results suggested that the infection of macrophages by leisbmanla is inhibited by PAF and enhanced by prostaglandins and that these mediators are produced by macrophages during this infection. This was confirmed by addition of these mediators to the culture medium before infection; PAF (10 -6, 10 -9 and 10-1Z M) reduced significantly the infection whereas PGEz (10-M) induced a marked enhancement. This effect of exogenous PAF on macrophage infection was reversed by the two PAF antagonists used in this study as well as by the inhibitor of nitric oxide synthesis, L-arginine methyl ester (100 mM). Taken together the data suggest that endogenous production of PAF and PGE2 exert opposing effects on Lesbmana-macrophage interaction and that nitric oxide may be involved in the augmented destruction of parasites induced by PAF.
Leishmania (L.) amazonensis-induced inhibition of nitric oxide synthesis in host macrophages
Microbes and Infection, 2002
Inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production was demonstrated in J774-G8 macrophages infected with Leishmania (L.) amazonensis promastigotes. The downmodulation of NO production observed in infected and LPS-stimulated J774-G8 cells correlated with a reduction in inducible nitric oxide synthase (iNOS) activity. Reduction in iNOS activity was not paralleled by decreased iNOS mRNA expression, suggesting that the parasite affects post-transcriptional events of NO synthesis. Supplementation with L-arginine or tetrahydrobiopterin did not increase NO production, suggesting that inhibition is not due to an insufficiency of substrate or co-factor. Treatment with anti-IL-10, anti-IL-4 or anti-TGF-neutralizing antibodies also failed to increase NO production, indicating that these cytokines are not involved in the observed parasite-induced inhibition of NO synthesis. However, treatment of the cultures with IFN-γ resulted in a marked increase in NO production by infected LPS-stimulated cells. These results show that although L.(L.) amazonensis infection inhibits iNOS activity and NO production by J774-G8 cells, activation by IFN-γ is capable of overriding the suppression of NO synthesis.
The Southeast Asian journal of tropical medicine and public health, 2009
Cutaneous leishmaniasis is still one of the health problems in Iran and in the region. Nitric oxide (NO) has a key mechanism in the elimination of parasite from the body by its anti-leishmanial activity. Prostaglandin (PG) is a critical inhibitory factor of infected macrophage to decrease their anti-leishmanial activity. This study was designed to induce NO by L-arginine (L-Arg) precursor and inhibit PG production by anti-inflammatory Indomethacin (INDO) in Leishmania major infected Balb/c mice, in order to evaluate the effects of NO and PG on delay of lesion formation, size of lesion and proliferation of amastigotes inside macrophages. Liver, spleen and lymph nodes were also studied as target organs to detect amastigotes. Serum, liver and spleen suspensions were investigated for NO induction by using Griess microassay and serum PG was determined by ELISA. The results indicated that NO production was inhibited by Leishmania in infected Balb/c mice as compared with naive animals. Ser...
Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide
The American journal of tropical medicine and hygiene, 2007
The requirements for effective and efficient intracellular killing of Leishmania amazonensis by activated macrophages are unknown. Despite resistance to the arginase inhibitor LOHA by intracellular L. amazonensis amastigotes, enhanced replication did not account for the relative resistance of this parasite to macrophage activation. Herein we report that the presence of both superoxide and nitric oxide is necessary for efficient killing of L. amazonensis amastigotes within LPS/IFN-gamma-activated bone marrow-derived macrophages generated from C3H mice. Addition of an extracellular signal-regulated kinase (ERK) inhibitor to L. amazonensis-infected macrophages increased the ability of these activated macrophages to kill L. amazonensis amastigotes. This enhanced macrophage killing through addition of ERK inhibitor was abrogated by inhibition of superoxide or iNOS, whereas inhibiting superoxide had no effect on the killing of L. major. These results suggest that ERK activation may modula...
Iranian journal of parasitology
The present study was conducted to investigate the optimized timing for macrophages induction and nitric oxide (NO) production against invading Leishmania parasite. The present study examined the murine macrophage cell line, B10R, in three different states. In the first state, the cells were first infected with L. major and then treated with IFN-γ and LPS as stimulants. In the second state, the cells were infected after stimulation with IFN-γ and LPS. In the third state, the cells were only exposed to stimulants as controls. In all the three states, cell culture supernatants were collected at three points in time (6, 24 and 48 h) and the amount of NO production was measured using Griess assay. The treatment of macrophages with inducers prior to infection with stationary phase parasite led to the secretion of significant amounts of NO, particularly at early time points quit contrary to the cells infected with parasites prior to induction. The amount of NO produced by cells induced af...
Repeated induction of nitric oxide synthase and leishmanicidal activity in murine macrophages
European Journal of Immunology, 1993
Murine macrophages express high levels of nitric oxide (NO) synthase and produce large amounts of NO when stimulated with interferon-y plus lipopolysaccharide in vitro. The expression of NO synthase peaks at 12 h after stimulation and declines rapidly to the background level by 72 h.These macrophages can be repeatedly reactivated to express similar levels of NO synthase. The reactivation is not due to newly divided cells since peritoneal macrophages which do not divide in vitro and 5774 cells cultured in the presence of colchicine can also be restimulated to express NO synthase. The reactivation is accompanied by re-expression of NO synthase mRNA, as assessed by polymerase chain reaction analysis. Furthermore, the reactivated macrophages are fully capable of killing the intracellular protozoan parasite Leishmania major. ~ A F. Q. C. is on leave from the
Production of nitric oxide by murine macrophages induced by lipophosphoglycan of Leishmania major
The Korean Journal of Parasitology, 2006
Protozoan parasites of genus Leishmania cause a number of important human diseases including cutaneous, mucocutaneous and visceral leishmaniasis. During their digenetic life cycle, these parasites alternate between an extracellular promastigote stage and an intracellular amastigote stage that reside within the phagolysosome compartment of macrophages in mammalian hosts (Descoteaux and Turco, 2002; Handman and Bullen, 2002). One of the key determinants of parasite infectivity and survival in these environments is the glycoconjugate lipophosphoglycan (LPG). LPG from all Leishmania species has same structure and composed of a repeating phosphorylated disaccharide unit attached via a phosphosaccharide core to the phosphatidylinositol, 1-O-alkyl-2-lysophosphatidylinositol (McConville et al., 1992; Turco and Descoteaux, 1992). New strategies for control of leishmaniasis are needed since chemotherapy such as antimonial drugs is prolonged, expensive, associated with side effects and relapses. Vector control has limitations and a vaccine which may be the best approach is not available. LPG has several functions and has been implicated in binding of parasites to epithelial cells of the sandfly
Oxidative Responses of Human and Murine Macrophages During Phagocytosis ofLeishmania chagasi
The Journal of Immunology, 2001
Leishmania chagasi, the cause of South American visceral leishmaniasis, must survive antimicrobial responses of host macrophages to establish infection. Macrophage oxidative responses have been shown to diminish in the presence of intracellular leishmania. However, using electron spin resonance we demonstrated that murine and human macrophages produce O2− during phagocytosis of opsonized promastigotes. Addition of the O2− scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl to cultures resulted in increased infection, suggesting that O2− enhances macrophage leishmanicidal activity. The importance of NO· produced by inducible NO synthase (iNOS) in controlling murine leishmaniasis is established, but its role in human macrophages has been debated. We detected NO· in supernatants from murine, but not human, macrophages infected with L. chagasi. Nonetheless, the iNOS inhibitor NG-monomethyl-l-arginine inhibited IFN-γ-mediated intracellular killing by both murine and human macrophage...