Félix C. Coulombié

Vesicular stomatitis virus induces apoptosis at early stages in the viral cycle and does not depend on virus replication.

We detected apoptosis induction in the vesicular stomatitis virus (VSV) infected mammalian cell lines Vero-76, Cos-7, and BHK-21. Cell lines were analyzed by chromosomal DNA fragmentation and nuclear morphology. In order to determine the step in the viral cycle at which apoptosis of infected cells is triggered, chemical and physical agents were used to block viral infection at different times and then the apoptotic response of infected cells was examined. The treatment of Vero-76 infected cells with a lysosomotrophic agent, such as NH4Cl, was shown to abrogate virus apoptosis induction. On the other hand, VSV-induced apoptosis was not blocked by the presence of cycloheximide, suggesting that the de novo viral protein synthesis is not required for this process. UV-inactivated viruses were also capable of inducing apoptosis in Vero-76 cells, indicating that the activation of a programmed cell death process by VSV does not require viral replication. We conclude from these findings that VSV induces apoptosis at early stages of infection.

Immunomodulatory activities of Cedrela tubiflora leaf aqueous extracts

Human peripheral blood monocytes and polymorphonuclear leukocytes treated with leaf aqueous extracts of the Meliaceae tree Cedrela tubiflora showed a diminution in both their phagocytic and respiratory burst activities. Besides, the extract inhibited the proliferation of Concanavalin A stimulated lymphocytes. A decrease in the hemolytic capacity of the human complement was also observed. The significance of the inhibitory effect observed over some components of the human immune system closely related with the inflammatory process is discussed.

Effect of Melia azedarach L. leaf extracts on human complement and polymorphonuclear leukocytes

The effect of the water extract of Melia azedarach L. (Meliaceae) leaves on human complement and polymorphonuclear leukocytes was investigated. This extract showed a strong anticomplementary activity, which was more pronounced in the classical pathway assay. The extract did not affect the phagocytic activity of polymorphonuclear leukocytes, nor the respiratory burst of these cells as measured by the nitro blue tetrazolium reduction assay.

Immunomodulatory activities of Cedrela lilloi and Trichilia elegans aqueous leaf extracts

The effects of Cedrela lilloi and Trichilia elegans (Meliaceae) aqueous leaf extracts on several parameters of the mouse immune system were studied. Both extracts showed a strong anticomplementary activity and inhibited the phagocytosis of opsonized sheep erythrocytes and the activation of the oxidative metabolism by opsonized zymosan on peritoneal macrophages. The in vitro proliferation of spleen T-lymphocytes was also impaired. Furthermore, treatment of mice with the extracts diminished the delayed-type hypersensitivity response to sheep erythrocytes. These results suggest that both extracts exert a marked immunomodulatory effect on the mouse immune system.

In vitro antiphagocytic effect of Melia azedarach leaf extracts on mouse peritoneal exudate cells

The effect of Melia azedarach L. (Meliaceae) leaf extract on the phagocytic capability and respiratory burst of mouse peritoneal exudate cells was studied. The extract inhibited the phagocytosis of opsonized sheep erythrocytes. This inhibition was both dose- and time-dependent and reverted 48 h after removing the extract from the culture medium. Furthermore, chemiluminescence in treated cells was also impaired using either receptor (opsonized zymosan) or post-receptor (PMA) stimuli.

In vitro and in vivo activities of Melia azedarach L. aqueous leaf extracts on murine lymphocytes

The effect of Melia azedarach L. aqueous leaf extracts (Ma) on in vitro lymphocyte proliferation and humoral and cellular immune responses in vivo was studied. Proliferation of spleen and lymph node T cells was impaired when these cells were incubated in the presence of the extract using different mitogens as stimuli. Furthermore, treatment of mice with the extracts not only diminished the production of antibodies but also exerted an inhibition on graft vs host and delayed type hypersensitivity reactions. These results suggest that Ma extracts exert a marked immunomodulatory effect on the mouse immune system.

In vitro activities of Cedrela tubiflora aqueous leaf extracts on murine macrophages, polymorphonuclear leukocytes and complement

Cedrela tubiflora aqueous leaf extracts are capable of inhibiting in vitro the activity of some components of the mouse immune system related to inflammatory responses. A significant reduction in the phagocytic capability and respiratory burst response (61.5% and 57.6%, respectively) of murine peritoneal macrophages was observed when these cells were incubated for 24 h with medium containing 1 mg/mL extract. On the other hand, at a concentration of 4 mg/mL, the extract reduced significantly the phagocytic activity of mouse polymorphonuclear leukocytes (87.5%) without altering the oxidative metabolism of these cells. Finally, a concentration of 2 mg/mL was required to inhibit the haemolytic activity of both pathways of mouse complement.

Oxidative Stress in Vero Cells Infected with Vesicular Stomatitis Virus

Viral-induced apoptosis might be mediated by oxidative stress. It has already been described that cell death in vesicular stomatitis virus (VSV)-infected cells occurs by apoptosis. In this study, oxidative stress parameters present in VSV-infected Vero cells were analyzed. Lipid peroxides (LP) were evaluated in cellular extracts and expressed as thiobarbituric acid-reactive substances. LP levels exhibited a rise at different times post infection, according to the multiplicity of infection (MOI), while the presence of cycloheximide determined a reduction on LP. Also, an increase in protein degradation products and a decrease in polyunsaturated fatty acids content was observed, indicating that cellular proteins and lipids began to be susceptible to degradation during VSV infection. In addition, we analyzed cell viability of VSV-infected Vero cells, which were incubated in the presence of butylated hydroxyanisole. This antioxidant was able to protect Vero cells, at least at MOIs assayed in this study, and to reduce viral yield only when VSV infection was done at MOI 0.05. Further, superoxide dismutases, which occupy the first step within the antioxidant enzyme cascade, also exhibit a rise in VSV-infected Vero cells, at different MOI. These results suggest that both an oxidative stress and an antioxidative cell response precede the induction of apoptosis by VSV.

Immunomodulatory activities of Trichilia glabra leaf aqueous extracts

Human peripheral blood monocytes and polymorphonuclear leukocytes treated with leaf aqueous extracts of the Meliaceae tree Trichilia glabra showed a diminution in both their phagocytic and respiratory burst activities. A decrease in the haemolytic capacity of the human complement was also observed.

Administration of Antithymocyte Serum Modifies the Response of Calomys musculinus to Junin Virus Infection

Approximately 80% of Calomys musculinus inoculated with an attenuated strain of Junin virus (JV) developed a lethal encephalitis. Antithymocyte serum, a potent suppressor of T-cell-mediated immunity, was studied for its effect on JV pathogenicity. Early administration of an anti-C. musculinus thymocyte serum (ACTS) to neonatal animals significantly diminished clinical disease and death and abrogated brain damage, which is usually associated with viral presence in the brain. Late ACTS administration did not modify the pattern of JV infection. These results suggest that immune mechanisms participate in the pathogenesis of JV infection for its main natural host.