concanavalin-a and Infections

Unbalanced Th1/Th2 T-cell responses in the liver are a characteristic of hepatic inflammation and subsequent liver fibrosis. The recently discovered Th17 cells, a subtype of CD4(+) T-helper cells mainly producing IL-17 and IL-22, have initially been linked to host defense against infections and to autoimmunity. Their preferred differentiation upon TGFβ and IL-6, two cytokines abundantly present in injured liver, makes a contribution of Th17 cells to hepatic inflammation very likely. Indeed, initial studies in humans revealed activated Th17 cells and Th17-related cytokines in various liver diseases. However, functional experiments in mouse models are not fully conclusive at present, and the pathogenic contribution of Th17 cells to liver inflammation might vary upon the disease etiology, for example, between infectious and autoimmune disorders. Understanding the chemokines and chemokine receptors promoting hepatic Th17 cell recruitment (possibly CCR6 or CCR4) might reveal new therapeutic targets interfering with Th17 migration or differentiation in liver disease.

Topics: Animals; Autoimmune Diseases; Autoimmunity; Cell Differentiation; Cell Movement; Chemical and Drug Induced Liver Injury; Concanavalin A; Disease Models, Animal; Humans; Infections; Inflammation; Interleukin-17; Interleukin-22; Interleukins; Liver; Liver Diseases; Mice; Receptors, Chemokine; T-Lymphocytes, Regulatory; Th17 Cells; Transforming Growth Factor beta

Topics: Animals; Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Concanavalin A; Disease Models, Animal; Galactosamine; Humans; Infections; Lipopolysaccharides; Liver Diseases; Tumor Necrosis Factor-alpha

The ability of bacteria to form biofilms hinders any conventional treatment for chronic infections and has serious socio-economic implications. For this purpose, a nanocarrier capable of overcoming the barrier of the mucopolysaccharide matrix of the biofilm and releasing its loaded-antibiotic within this matrix would be desirable. Herein, we developed a new nanosystem based on levofloxacin (LEVO)-loaded mesoporous silica nanoparticles (MSN) decorated with the lectin concanavalin A (ConA). The presence of ConA promotes the internalization of this nanosystem into the biofilm matrix, which increases the antimicrobial efficacy of the antibiotic hosted within the mesopores. This nanodevice is envisioned as a promising alternative to conventional treatments for infection by improving the antimicrobial efficacy and reducing side effects. STATEMENT OF SIGNIFICANCE: The present study is focused on finding an adequate therapeutic solution for the treatment of bone infection using nanocarriers that are capable of overcoming the biofilm barrier by increasing the therapeutic efficacy of the loaded antibiotic. For this purpose, we present a nanoantibiotic that increases the effectiveness of levofloxacin to destroy the biofilm formed by the model bacterium E. coli. This work opens new lines of research in the treatment of chronic infections based on nanomedicines.

Topics: Animals; Cell Line; Concanavalin A; Infections; Levofloxacin; Mice; Nanoparticles; Porosity; Silicon Dioxide

immunodepression after stroke is associated with complications like high infection rate, but its role in aneurysmal subarachnoid hemorrhage (aSAH) is unclear. This pilot study aimed to assess the presence of immunodepression and its association with infections after aSAH.. sixteen aSAH patients were enrolled in a prospective study on immune function in a single institution. Detailed immune monitoring (peripheral blood leukocyte subsets, monocyte human leukocyte antigen-DR expression, ex vivo lipopolysaccharide-induced monocytic, Concanavalin A-induced lymphocytic cytokine secretion) was performed until day 10 after aSAH. Occurrence of infection was assessed within 14 days after aSAH.. sixteen consecutive aSAH patients (53.1 ± 10.2 years; mean ± SD) met the inclusion criteria, classified as asymptomatic (World Federation of Neurological Surgeons; median, 1; quartile, 1-1; n=7) and symptomatic (median, 4; quartile, 3-5; n=9), all presenting with acute neurological deficits, and 5 of these had additional delayed cerebral ischemia. T-lymphopenia, impaired ex vivo lymphocytic/monocytic cytokine secretion, and decreased monocyte human leukocyte antigen-DR expression occurred over all World Federation of Neurological Surgeons grades but persisted beyond day 3 only in symptomatic patients. Pneumonia (67%; P=0.011) was more frequent in symptomatic patients. Already at day 1, patients with pneumonia showed significantly lower T-cell counts and mitogen-induced interferon-γ production compared to patients without infections.. a pronounced SAH-induced immunodepression was observed early after aSAH but persisted only in symptomatic patients. Immunodepression was associated with a high incidence of pneumonia. Early diagnosis of immunodepression might allow targeted treatment to prevent infectious complications after aSAH.

Topics: Adult; Cells, Cultured; Concanavalin A; Female; Gene Expression Regulation; HLA-DR Antigens; Humans; Immune Tolerance; Infections; Interferon-gamma; Lipopolysaccharides; Lymphocytes; Male; Middle Aged; Mitogens; Monocytes; Pneumonia; Prospective Studies; Subarachnoid Hemorrhage; Time Factors

Preoperative autologous blood donation (PABD) has been shown to decrease natural killer (NK) cell function in cancer patients, raising concerns about an increased cancer recurrence risk owing to PABD. It is unclear whether PABD leads to other immunomodulatory effects that might affect more short-term risks like postoperative infectious complications in surgical patients. Lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells, NK cells) were determined in 86 consecutive patients donating 2 units of autologous whole blood prior to elective hip replacement surgery. In addition, cytokine secretion patterns of monocytes [tumour necrosis factor (TNF)] and lymphocytes [interferon-gamma, interleukin (IL)-2, IL-4, IL-10] upon stimulation were determined in a random subgroup of 58 patients. Analyses were performed immediately before the first donation and on the day prior to operation. Granulocytes increased during PABD by 4.6% (P < 0.01). Lymphocytes decreased by 8.8% (P < 0.01), accompanied by a relative rise in CD4+ T cells by 10.7% (P < 0.01) and in B cells by 10.3% (P < 0.01), and a fall of NK cells by 20.8% (P < 0.01). Stimulated TNF secretion of monocytes was suppressed (-12.3%, P < 0.01). The effect on the reactivity of lymphocytes and the T helper 1 (Th1)/Th2 balance were variable. The observed changes of innate and cellular immunity might influence the risk of perioperative infectious complications.

Topics: Aged; Arthroplasty, Replacement, Hip; Blood Donors; Blood Transfusion, Autologous; Cells, Cultured; Cohort Studies; Concanavalin A; Cytokines; Disease Susceptibility; Elective Surgical Procedures; Female; Humans; Immunity, Cellular; Immunocompromised Host; Infections; Iron; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Subsets; Male; Middle Aged; Monocytes; Phytohemagglutinins; Postoperative Complications; Preoperative Care; Sampling Studies; Th1 Cells; Th2 Cells

The presence of increased levels of suppressor T cells after thermal injury and their relevance remain controversial. It is unclear whether suppressor T cells are the cause or result of sepsis complicating thermal injury. Spleen cells from a standardized murine burn model and sham burn controls were studied and the relationship between the levels of suppressor cytotoxic T cells (CD8, Lyt-2+), helper T cells (CD4, L3T4+), response to concanavalin A (ConA) and to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production was examined. Mortality following infection via cecal ligation and puncture (CLP) of matched controls was also studied. At day 7 postburn, mean ConA (70 +/- 12% of control) and PHA response (58% +/- 5.2% of controls) and IL-2 production (43% +/- 5.4%) were significantly less than sham burn values (100%; p less than 0.05). However, the mean percentage of cells staining with anti-Lyt-2 and anti-L3T4 (9.1 +/- 0.59 and 13.9 +/- 0.65) was similar to the mean percentage in sham burn animals (9.4 +/- 0.65 and 16.6 +/- 1.1). Furthermore, no significant differences were observed between burned mice and controls in helper (17.3% +/- 1.8% burn vs. 21.2% +/- 1.7% sham) or suppressor cell levels (7.8% +/- 1.2% burn vs. 8.6% +/- 0.7% sham) or helper-suppressor ratios on day 10 postburn. Mortality of 20 litter-matched controls subjected to CLP on day 10 postburn was 90%, which was significantly greater than the sham burn mortality of 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antibodies, Monoclonal; Biomarkers; Burns; CD4-CD8 Ratio; Concanavalin A; Disease Models, Animal; Evaluation Studies as Topic; Immunologic Deficiency Syndromes; Infections; Interleukin-2; Lymphocyte Activation; Male; Mice; Phenotype; Phytohemagglutinins; Predictive Value of Tests; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

To determine whether hemorrhage without major tissue trauma can itself produce immunosuppression, the effect of hemorrhage on the lymphocyte response to T-cell mitogen in endotoxin-resistant C3H/HEJ mice was measured. The mice were bled to achieve a mean blood pressure of 35 mm Hg, maintained at that level for one hour, and then adequately resuscitated. On days 1 through 10 thereafter, the proliferative responses of the splenocytes to concanavalin A were measured and allogeneic mixed lymphocyte reaction was performed. The proliferative responses to mitogen stimulation as well as the results of mixed lymphocyte reaction studies indicated that marked immunosuppression occurred at day 1. Immunosuppression persisted for at least five days following hemorrhage, as evidenced by mitogen stimulation assay. Another group of mice was subjected to sepsis three days after hemorrhage and resuscitation. The mortalities in the sham-hemorrhage and hemorrhage groups following sepsis were 58% and 100%, respectively. Thus, a significant depression of cellular immunity occurred following simple hemorrhage despite adequate resuscitation, and this immunosuppression enhanced the susceptibility to sepsis.

Topics: Animals; Concanavalin A; Disease Models, Animal; Disease Susceptibility; Hemorrhage; Immunity, Cellular; Immunosuppression Therapy; Infections; Lymphocyte Activation; Mice; Mice, Inbred C3H; Spleen; Time Factors

The heterogeneity of gamma-glutamyltranspeptidase (GGT) in seminal plasma has been studied using Con A-chromatography. This parameter was then related to the fructose concentration, the acid phosphatase activity, ejaculate volume, sperm density and the number of bacteria per ml. Multivariate regression analysis and stepwise elimination of the least fitting factors, revealed that Con A-binding correlated with the number of bacteria per ml of semen and the acid phosphatase activity with 49% of the variance of GGT-binding being explained by these parameters. This result suggests that glycosylation of seminal GGT is altered by accessory gland infection. Neuraminidase digestion suggests that the pattern of Con A-binding of seminal GGT depends only partly on its sialic acid content.

Topics: Acid Phosphatase; Carbohydrate Metabolism; Chromatography, Affinity; Concanavalin A; gamma-Glutamyltransferase; Genital Diseases, Male; Humans; Infections; Male; Neuraminidase; Prostatitis; Semen

Chronic alcoholics are more susceptible to infection and have increased incidences of certain types of carcinomas. One explanation for this may be suppressed immune responses secondary to ethyl alcohol consumption. This project was initiated to study the effect of ethyl alcohol on lymphocyte responses in vitro by monitoring tritiated thymidine uptake. Lymphocytes were incubated in the presence of phytohemagglutinin-P, concanavalin A, and pokeweed mitogen. The response of normal lymphocytes was noted after mitogen stimulation in the presence of ethyl alcohol in graded doses. Ethyl alcohol levels greater than or equal to 50 mg/dL suppressed tritiated thymidine uptake of normal lymphocytes for phytohemagglutinin-P and concanavalin A. Since ethyl alcohol exposure in concentrations consistent with blood levels that may be attained during routine ingestion significantly decreased lymphocyte blastogenesis, it is speculated that chronic ethyl alcohol ingestion may alter immune surveillance sufficiently to be responsible in part for the increased incidence of infection and/or neoplasms seen in alcoholic subjects.

Topics: Adult; Alcoholism; Concanavalin A; Dose-Response Relationship, Drug; Ethanol; Female; Humans; Infections; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Neoplasms; Phytohemagglutinins; Pokeweed Mitogens; Stimulation, Chemical; Thymidine

Cell-mediated immunity was examined using 4 recall antigens in 102 critically ill surgical patients treated in an ICU. There were 4 (14%) deaths in 28 patients with positive reactions (R), compared to 33 (45%) deaths in 74 nonreactors (NR) (p less than .01). Thirty-seven of the patients were admitted after trauma, and mortality in this group was not significantly different between R and NR patients. Repeat testing in 40 NR patients who remained in the ICU for more than 7 days showed that 30 remained NR (70% mortality) and 10 became R (20% mortality, p less than .001). Peripheral blood lymphocytes from the patients showed a reduced response to concanavalin A, but a normal response to phytohemagglutinin and pokeweed mitogen. Mononuclear cells and granulocytes both showed a small increase in chemotactic response to casein, suggesting that the reduced response to skin testing may be partly due to defective T-cell function, rather than impaired phagocyte chemotaxis.

Topics: Adolescent; Adult; Aged; Chemotaxis, Leukocyte; Concanavalin A; Female; Humans; Immunity, Cellular; Infections; Lymphocyte Activation; Male; Middle Aged; Monocytes; Neutrophils; Phytohemagglutinins; Pokeweed Mitogens; Postoperative Complications; Skin Tests

In vitro lymphocyte response to antigens, mitogens and in mixed lymphocyte culture were studied at intervals after injury in 31 patients with extensive trauma. Mean responses were significantly depressed up to 15 to 20 days. Responses were lower and the duration of suppression longer in those patients who become infected, and the suppression of response preceded the onset of infection. Extremely low responses were found in three patients who later died. This in vitro system is suitable for the serial monitoring of patients, as it reflects the extent of injury, infectious sequelae and prognosis. Its results are quantifiable and avoid the problems associated with repeated skin testing.

Topics: Accidents, Traffic; Adult; Concanavalin A; Histocompatibility Antigens Class II; Humans; In Vitro Techniques; Infections; Lymphocytes; Mitogens; Mumps; Phytohemagglutinins; Risk; Streptodornase and Streptokinase; Time Factors; Wounds and Injuries

Topics: Concanavalin A; Humans; Infections; Inflammation; Interleukin-1; Neutrophils; Proteins; Thymus Gland

Schwachman's syndrome is characterised by pancreatic insufficiency and frequent infections. Absolute polymorphonuclear leucocyte (PMN) counts are low in many patients, and the PMN show abnormal chemotaxis. It was postulated that a cytoskeletal defect might underlie these abnormalities, and a cytoskeleton-dependent function, the surface distribution and mobility of concanavalin-A receptors, was studied on neutrophils from Schwachman's syndrome patients. Approximately a third of the neutrophils in each patient showed a patched distribution of fluorescein-conjugated concanavalin A (FITC-con A) rather than the usual diffuse staining pattern. These patched neutrophils also bound larger amounts of FITC-con A than diffusely stained or capped PMN from the same patient. Antitubulin treatment did not alter the proportion of patched PMN. These findings suggest that a cytoskeletal defect underlies the patching of FITC-con A on the PMN surface. This defect could also contribute to the abnormal chemotaxis and frequent infections found in Shwachman's syndrome patients.

Topics: Adolescent; Agranulocytosis; Cell Membrane; Chemotaxis; Child, Preschool; Concanavalin A; Cytoskeleton; Disease Susceptibility; Exocrine Pancreatic Insufficiency; Humans; Infections; Neutropenia; Neutrophils; Receptors, Concanavalin A; Staining and Labeling; Syndrome

Patients with most forms of protein-calorie malnutrition are typically more susceptible to infection. We studied the immunological consequences of a subgroup of malnourished subjects--nine patients with anorexia nervosa, who typically have a lower incidence of infection. The profiles of the patients with anorexia nervosa deviated from the reported typical profile of significantly depressed cell-mediated immunity in subjects with more common forms of protein-calorie malnutrition, demonstrating normal T-lymphocyte populations and unimpaired proliferative lymphocyte responsiveness to mitogenic stimulation with phytohemagglutinin and concanavalin A. In fact, mitogen responsiveness was significantly elevated above that of controls, and with nutritional repletion, this enhanced responsiveness regressed toward control values. Since impaired cell-mediated immunity has been consistently documented in other malnourished populations, and presumably contributes to their increased propensity toward infection, the maintenance of a relatively intact cell-mediated immune system may be an important factor separating the malnourished anorexia nervosa patient from other protein-calorie malnourished patients.

Topics: Adolescent; Adult; Anorexia Nervosa; Concanavalin A; Female; Humans; Immunity, Cellular; Infections; Lymphocyte Activation; Male; Phytohemagglutinins; Protein-Energy Malnutrition; Skin Tests; T-Lymphocytes

The function of lymphocytes and monocytes was compared in a group of 18 ex-sandblasters with silicosis and 19 control subjects. Previously noted depressed lymphocytic proliferation in response to low concentrations of concanavalin A (ConA) in subjects with silicosis was not due to factors in the serum nor correctable by supplementation with allogeneic lymphocytes. Monocytes from the peripheral blood of the subjects with silicosis responded less to a chemotactic stimulus (zymosan-activated serum) than did monocytes from normal laboratory personnel; however, there was no difference in monocytic chemotaxis when groups of similar age were compared. There was a significant correlation between age and the monocytic response to chemotactic stimuli in the studied population (laboratory personnel, silicotic subjects, and age-matched control subjects). Overall, our data suggest subtle effects of silica on selected T-lymphocytic populations involved with responsiveness to the mitogen, concanavalin A, but no effects on monocytic function. Monocytic chemotaxis is unaffected by exposure to silica but is inversely related to age.

Topics: Age Factors; Cell Division; Chemotaxis; Concanavalin A; Humans; Infections; Middle Aged; Mitogens; Monocytes; Silicosis; T-Lymphocytes