RESUMEN
Splenectomized mice control Listeria monocytogenes infection better than non-splenectomized mice. Here, BALB/c mice subjected to splenectomy and autogenous grafting of spleen were evaluated after 3 and 7 days of intravenous L. monocytogenes infection. The group of splenectomized animals (SP) presented a lower number of bacteria in the liver in comparison with both the sham-operated control group (CT) and the group that received splenic autotransplantation (AT) in the retroperitoneal site. The AT group presented bacterial counts in the liver similar to the CT group. SP animals showed larger production of interferon-gamma (IFN-γ) and nitric oxide (NO) in the liver in comparison with CT and AT, this being associated with greater accumulation of mononuclear cells. IFN-γ production by spleen cells after stimulation with heat-killed Listeria was similar between the AT and CT groups, suggesting that the implanted fragments behaved like the original organ. The autogenous grafting of spleen fragments reverses the resistance to L. monocytogenes infection found in splenectomized mice, associated with a reduced IFN-γ and NO production in the liver. The present study shows that splenic autotransplantation restores the function of the spleen in splenectomized mice, even though in this case it does favor the susceptibility to L. monocytogenes infection.
Asunto(s)
Interferón gamma/metabolismo , Listeria monocytogenes , Listeriosis/inmunología , Óxido Nítrico/metabolismo , Bazo/trasplante , Esplenectomía , Animales , Interferón gamma/genética , Listeriosis/microbiología , Listeriosis/patología , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Endogámicos BALB CRESUMEN
The high incidence of overwhelming postsplenectomy infection caused by Streptococcus pneumoniae can be reduced by splenic autotransplantation. In this study the effect of splenectomy and splenic autotransplantation on the immune response to S. pneumoniae infection was investigated. Balb/c mice were divided into three groups: splenectomized (SP), splenectomized and autotransplanted (AT), and sham operated control (CT). Five days post-infection the serum antibody levels were measured and the number of S. pneumoniae CFU, neutrophil accumulation and IL-17 production in the liver and lungs were investigated. SP mice showed greater number of bacteria in both organs and lower serum levels of S. pneumoniae-specific IgM, IgG1 and IgG2a antibodies. IL-17 production and neutrophil recruitment to the liver and lungs were lower in SP mice, in comparison with both the CT and the AT groups. Levels of S. pneumoniae-specific IgM, CFU counts, neutrophil accumulation and IL-17 production did not differ significantly between the CT and AT groups. These results suggest that splenic autotransplantation restores the capacity of splenectomized mice to fight S. pneumoniae infection.
Asunto(s)
Hígado/inmunología , Pulmón/inmunología , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Movimiento Celular , Recuento de Colonia Microbiana , Inmunidad , Interleucina-17/inmunología , Interleucina-17/metabolismo , Hígado/metabolismo , Hígado/microbiología , Hígado/patología , Pulmón/metabolismo , Pulmón/microbiología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Neutrófilos/patología , Infecciones Neumocócicas/sangre , Infecciones Neumocócicas/cirugía , Infecciones Neumocócicas/terapia , Esplenectomía/efectos adversos , Streptococcus pneumoniae/crecimiento & desarrollo , Streptococcus pneumoniae/patogenicidad , Trasplante Autólogo , VirulenciaRESUMEN
BACKGROUND: Photodynamic therapy (PDT) has been described for photoageing treatment, but its mechanism of action is not clarified. Although PDT-induced matrix metalloproteinase (MMP) expression and collagen production have been studied in normal skin and in inflammatory disease, there is no report about the effect of PDT on the extracellular matrix in photodamaged skin. OBJECTIVES: To evaluate skin remodelling induced by methyl aminolaevulinate (MAL)-PDT in photodamaged skin by histological and immunohistochemical studies. METHODS: Fourteen patients were treated with two sessions of MAL-PDT. The light source was a light-emitting diode (635 nm, 37 J cm(-2)). Skin biopsies were performed in all patients before and at 3 and 6 months after treatment. Immunohistochemical studies evaluated collagen types I and III, MMP-1, MMP-3, MMP-7, MMP-9, MMP-12 and tissue inhibitor of metalloproteinases-1. RESULTS: Global improvement in photodamaged skin was observed. A significant increase in expression of MMP-9 in the dermis was detected at 3 months after treatment (P = 0.002). Significant increases in the expression of collagen type I at 3 months (P = 0.002) and at 6 months after treatment (P = 0.001) were also observed. CONCLUSIONS: Skin remodelling induced by MAL-PDT was demonstrated in photodamaged skin. Two sessions of MAL-PDT increases immunohistochemical expression of MMP-9 in the dermis at 3 months after treatment, and also of collagen type I.
Asunto(s)
Metaloproteinasas de la Matriz/biosíntesis , Fotoquimioterapia , Envejecimiento de la Piel , Piel/metabolismo , Ácido Aminolevulínico/análogos & derivados , Ácido Aminolevulínico/uso terapéutico , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Femenino , Humanos , Inmunohistoquímica , Terapia por Luz de Baja Intensidad , Masculino , Persona de Mediana Edad , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/patología , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
Splenectomy results in an increased risk of sepsis. The autogenous transplant of the spleen is an option for preserving splenic functions after total splenectomy. In this study, the capacity of animals undergoing autogenous spleen transplantation to respond to Staphylococcus aureus infection was investigated. BALB/c mice were divided into three groups: splenectomy followed by autotransplantation in the retroperitonium (AT), splenectomized only (SP) and operated non-splenectomized sham control (CT). Thirty days after surgery the mice were infected intravenously with S. aureus. Splenectomized mice had a higher number of colony-forming units (CFU) of S. aureus in liver and lungs in comparison with either AT or with CT mice (P < 0.05). Higher CFU numbers in lung of SP mice correlated with elevated production of interleukin-10 associated with a lower production of interferon-gamma and tumour necrosis factor-alpha. However, systemically, the level of tumour necrosis factor-alpha was higher in the SP group than in CT or AT. Lower titres of specific anti-S. aureus immunoglobulin (Ig)M and IgG1 were observed 6 days after infection in SP mice in comparison either with the AT or CT groups. Thus, splenectomy is detrimental to the immune response of BALB/c mice against infection by S. aureus which can be re-established by autogenous implantation of the spleen.