Galectinas: una nueva familia de proteínas involucradas en la regulación de la respuesta inmune. Implicancias en procesos inmunopatológicos / Galectins: a novel family of proteins involved in the regulation of the immune response. Implications in immunopathological processes

Las galectinas constituyen una familia de proteínas extremadamente conservada a través de la evolución. En función de su propiedad de decifrar glicocódigos específicos, estas proteínas han sido involucradas en un amplio espectro de eventos biológicos. Recientes avances han demostrados que estas proteínas han juegan un rol fundamental en procesos relacionados a la regulación de la respuesta inmune, tales como adhesión linfocitaria, crecimiento celular, producción de citoquinas y regulación de la muerte celular progamada. En el presente artículo se analizan las implicancias de estas familias de proteínas en desórdenes autoinmunes, inflamación aguda y crónica, transtornos alérgicos, infecciones y enfermedades neoplásicas. La utilización de estas proteínas endógenas y sus antagonistas en el diagnóstico y tratamiento de estas patologías abre un nuevo horizonte en el campo de la inmunopatología molecular.

Galectins: a key intersection between glycobiology and immunology

Galectins are a family of evolutionarily conserved animal lectins, widely distributed from lower invertebrates to mammals. They share sequence and structure similarities in the carbohydrate recognition domain and specificity for polylactosamine-enriched glycoconjugates. In the last few years significant experimental data have been accumulated concerning their participation in different biological processes requiring carbohydrate recognition such as cell adhesion, cell growth regulation, inflammation, immunomodulation, apoptosis and metastasis. In the present review we will discuss some exciting questions and advances in galectin research, highlighting the significance of these proteins in immunological processes and their implications in biomedical research, disease diagnosis and clinical intervention. Designing novel therapeutic strategies based on carbohydrate recognition will provide answers for the treatment of autoimmune disorders, inflammatory processes, allergic reactions and tumor spreading.

Oral vaccine against cholera prepared from Vibrio cholerae antigen(s).

Albino rats aged 7-8 weeks old purchased from the National Laboratory Animal Centre, Salaya, Nakhon Pathom, were found to be a good animal model for the study on immunogenicity of V. cholerae antigens. Seventy-two rats were fasted for 15 hours before feeding each one with 1 ml of 5% NaHCO3 to reduce gastric acidity prior to immunization. They were divided into 9 groups of 8 rats and immunized orally with 2 ml, each, of the V. cholerae antigens dissolved or suspended in Cassamino acid as follows: group 1 (control): Cassamino acid (Ca) alone; group 2 (control): 2.5% formalinized sheep red blood cells (F-SRBC); group 3: 1,000 micrograms of lipopolysaccharide (LPS); group 4: 100 micrograms of procholeragenoid (P); group 5: 80 haemagglutinating units of cell-bound haemagglutinin (CHA) adsorbed onto the surface of F-SRBC (CH-SRBC); group 6: 500 micrograms of LPS + 50 micrograms of P; group 7: CH-SRBC + 50 micrograms of P; group 8: combined vaccine formula 1 consisted of 500 micrograms of LPS, CH-SRBC and 50 micrograms of P and group 9: combined vaccine formula 2 consisted of 1,000 micrograms of LPS, CH-SRBC and 100 micrograms of P. The immunization was repeated once more 14 days later. Five days, thereafter, the rats were killed and their jejuni were removed for cryostat sectioning. Antibody producing cells against LPS (anti-LPS cells), P (anti-CT cells) and CHA (anti-CHA cells) in the intestinal lamina propria were enumerated by double antibody sandwich method of immunofluorescence using pure LPS, cholera toxin (CT) and pure CHA as the antigens in the assay, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies against Vibrio cholerae lipopolysaccharide, cell-bound haemagglutinin and toxin in the intestinal fluid during convalescence.

Specific antibodies to V. cholerae lipopolysaccharide (LPS), cell-bound haemagglutinin (CHA) and toxin (CT) in the intestinal lavages of healthy Thais and Thai cholera patients during the convalescence period were determined by enzyme-linked immunosorbent assay. Only IgM and IgA specific antibodies were detectable in the specimens. All of the persons who were just recovered from cholera had IgA anti-CT and IgA anti-LPS and 82.4% had IgA anti-CHA. The IgA anti-CT, anti-LPS and anti-CHA were detected also in the gut fluids of 70.6%, 94.1% and 88.2%, respectively, of the healthy controls. The mean levels of the IgA antibodies of all specificities between the two groups of individuals were not different. However, the IgM anti-CT and IgM anti-LPS of the cholera patients increased during the convalescence period. The levels, therefore, were significantly higher than those of the controls. The ratios of IgA anti-CT: IgM anti-CT and IgA anti-LPS: IgM anti-LPS among the patients were 2.93:1 and 2.02:1, respectively while those of the controls were 10:1 and 34:1, respectively. IgA antibodies predominated in the lavages of both groups of the individuals.

Vibriocidal antibody and antibodies to Vibrio cholerae lipopolysaccharide, cell-bound haemagglutinin and toxin in Thai population.

Vibriocidal antibody and antibodies to Vibrio cholerae lipopolysaccharide (anti-LPS), cell-bound haemagglutinin (anti-CHA) and toxin (anti-CT) were determined in Thai individuals of various age groups who lived in areas with high (H) and low (L) cholera endemicity. The enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of class specific anti-LPS, anti-CHA and anti-CT. It was found that Thai individuals acquired the vibriocidal antibody early in life. Fifty percent of individuals aged 5 to 15 years old had detectable titre while more than 80% of adults had titres ranged from 1:5 to 1:125 or higher. Thai adults who lived in area with high cholera endemicity had significantly higher vibriocidal antibody levels than their counterparts who lived in area with low cholera endemicity. Lipopolysaccharide was not the only antigen responsible for stimulating the vibriocidal antibody production. Adult levels of all classes of anti-CHA from L were higher than those of H while the anti-LPS in the forms of total immunoglobulins, IgG and IgA were similar but IgM of L was higher than that of H. The levels of all classes of anti-CT from H seemed to increase with age except at the school age (5 years to 15 years old) when there were marked decreases of all antibody classes. Total immunoglobulin and IgM anti-CT at adult age of H and L were not different, although IgG anti-CT of L was higher than that of H and IgA anti-CT of H was higher than that of L.

Cell-bound haemagglutinin (CHA) of V. cholerae 01 as protective antigen.

The study of immunogenicity of cell-bound haemagglutinin (CHA) of Vibrio cholerae E1 Tor in mice revealed that the CHA was a good antigen when it was adsorbed onto the surface of sheep red blood cells and given orally to mice. The antigen not only induced high levels of various class antibodies which sustained in the intestinal tracts for a long period of time (longer than 6 months) but also the antibodies were protective against homologous cholera challenge. The degree of protection seems to correlate with the level of IgA in the intestinal washing. The protective ability was conferred mainly by anti-CHA.

Inhibitor to the cell-bound haemagglutinin of Vibrio cholerae.

An inhibitor to cell-bound HA was found to be produced at the non-haemagglutinating phase of the culture cycle by a classical vibrio strain which produced a cell-bound HA early and transiently during its growth. The HA-negative filtrate obtained from the late log-culture was found to inhibit the cell-bound HA activity produced by the same vibrio strain. It was also found to be produced early in shaking cultures at 37 degrees C and to mask the activity of early cell-bound HA in whole culture tests. This inhibitor is suggested to be responsible for the failure to obtain HA activity or adhesive vibrio cells grown at 37 degrees C and for the transient expression of cell-bound HA by some V. cholerae strains.

Immunogenicity of soluble haemagglutinin-lipopolysaccharide complex of classical vibrio cholerae.

Soluble haemagglutinin-lipopolysaccharide complexes were found to be good antigens since it elicited high levels of the antibodies in the intestine especially of the IgA class. These specific antibodies sustained for a long period of time at the significantly high levels (longer than 6 months). The enteric memory primed by the antigens in the intestinal tract were longer than 3 months. Pools of intestinal fluids obtained from mice immunized with single dose of SH-LPS at 1 week, 1 month and 3 months after the antigen stimulation conferred protection against the homologous challenge. Better protection was found in the corresponding specimens collected from mice which received antigen booster at 3 months after the first stimulation. Multiple oral doses of the antigens (three doses at weekly intervals) did not have any advantage over the single dose immunization. The intestinal fluids obtained from the former group conferred similar degree of protection as those from the latter though the serum specimens offered higher PD50. The protection against cholera does not correlate with the levels of vibriocidal antibody in the body fluids which seems to confirm the hypothesis that the mechanism of protection against cholera by intestinal antibody is by reducing or preventing the attachment of the vibrios to the epithelium either via agglutinating process or via masking of the vibrio adhesive sites.