concanavalin-a and Virus-Diseases

Prolonged, exhaustive exercise has been associated with impaired immune responsiveness and increased susceptibility to infection. We have shown that one bout of exercise to fatigue followed by viral challenge increases mortality. Stress hormones such as corticosteroids and catecholamines have been suggested as potential mediators of exhaustive exercise-induced immunosuppression. The purpose of this study was to determine whether the administration of pharmacological agents to block the effect of catecholamines or corticosteroids would minimize the immunosuppression associated with this type of exercise. Mice either exercised to fatigue or were exposed to control conditions, and mice received an i.p. injection of either nadolol (beta-adrenergic receptor antagonist), RU486 (glucocorticoid type II receptor antagonist), or vehicle. Fifteen minutes post-exercise, mice were exposed to viral infection (Herpes simplex virus; HSV) via an intranasal route, and cells were collected 3 days post-infection. The results showed that exercise suppressed HSV-specific cell proliferation, HSV-specific IL-2, and IFN-gamma, but did not alter these same immune parameters when the mitogen ConA was used to stimulate cells. In addition, exercise reduced NK cell cytotoxicity, alveolar cell TNFalpha, and peritoneal IL-1beta, but did not affect IL-10. The pharmacological blockade did not attenuate the exercise-associated immunosuppression. In fact, RU486 treatment exacerbated the exercise-induced decline in HSV-induced IL-2 production and cell proliferation. RU486 and nadolol treatment also tended to decrease IL-10, IFN-gamma, TNFalpha (nadolol only), and IL-1beta (RU486 only) in both exercise and control mice, suggesting that stress hormones may be necessary during infection for optimal responsiveness. These findings suggest that suppression of immune defenses during viral infection persists for at least 3 days post-exercise, and stress hormones may be essential for optimal immune defense to viral challenge, rather than detrimental.

Topics: Animals; Antigens, Viral; Catecholamines; Cell Proliferation; Cell Survival; Cells, Cultured; Concanavalin A; Cytokines; Glucocorticoids; Herpes Simplex; Herpesvirus 1, Human; Interleukin-2; Killer Cells, Natural; Macrophages, Peritoneal; Male; Mice; Mice, Inbred BALB C; Mitogens; Physical Exertion; Pulmonary Alveoli; Th1 Cells; Th2 Cells; Virus Diseases

To investigate whether activity and glucocorticoid treatment of rheumatic diseases are reflected by selected parameters of cellular energy metabolism of peripheral blood mononuclear cells (PBMC).. PBMC were obtained from 30 healthy volunteers, 28 patients (16 inactive; 12 active) with rheumatoid arthritis, systemic lupus erythematosus, vasculitis, or other autoimmune diseases, and five patients with infectious diseases. Patients with active rheumatic diseases were examined before and 4-5 days after starting, restarting, or increasing the dose of glucocorticoids. Cellular oxygen consumption (as a measure of ATP production), bioenergetic ability to be stimulated, and major ATP consuming processes were measured amperometrically with a Clark electrode.. A normal value for oxygen consumption of 3.84 (SEM 0.1) (all data in nmol O(2)/min/10(7) cells) independent of sex was found. In patients with inactive disease the respiration rate was slightly higher, but was significantly increased in active patients to 4.82 (SEM 0.33) (p<0.001). PBMC from active patients showed a significantly lower bioenergetic response to a mitogenic stimulus than controls (p<0.05). In stimulated cells from active patients there was a significant reduction in cation transport and protein synthesis. All parameters above were almost normalised within 4-5 days upon optimised treatment with glucocorticoids. For comparison, PBMC from patients with active infectious diseases also showed an increased respiration rate; their response to mitogenic stimulation was even higher.. This study shows for the first time that parameters describing the cellular function of PBMC in bioenergetic terms are suitable for (a) describing semiquantitatively the activity of a rheumatic disease and (b) assessing the therapeutic effect on the disease.

Topics: Adolescent; Adult; Aged; Antirheumatic Agents; Autoimmune Diseases; Cell Culture Techniques; Concanavalin A; Energy Metabolism; Female; Glucocorticoids; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Oxygen Consumption; Rheumatic Diseases; Treatment Outcome; Virus Diseases

T cell receptor stimulation without costimulation is insufficient for the induction of an optimal immune response. It is thought that engagement of the CD28 molecule with its ligand B7 provides an essential costimulatory signal without which full activation of T cells cannot occur. A mouse strain with a defective CD28 gene was established. Development of T and B cells in the CD28-deficient mice appeared normal. However, T lymphocytes derived from CD28-/- mutant mice had impaired responses to lectins. Lectin stimulation did not trigger interleukin-2 (IL-2) production, IL-2 receptor alpha expression was significantly decreased, and exogenous IL-2 only partially rescued the CD28 defect. Basal immunoglobulin (Ig) concentrations in CD28-deficient mice were about one-fifth of those found in wild-type controls, with low titers of IgG1 and IgG2b but an increase in IgG2a. In addition, activity of T helper cells in CD28-/- mice was reduced and immunoglobulin class switching was diminished after infection with vesicular stomatitis virus. However, cytotoxic T cells could still be induced and the mice showed delayed-type hypersensitivity after infection with lymphocytic choriomeningitis virus. Thus, CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist.

Topics: Animals; Antibodies, Viral; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; B-Lymphocytes; B7-1 Antigen; CD28 Antigens; Concanavalin A; Immunoglobulins; Interleukin-2; Lymphocyte Activation; Lymphocytic Choriomeningitis; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Mutant Strains; Mutation; Receptors, Interleukin-2; T-Lymphocytes; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer; Vesicular stomatitis Indiana virus; Virus Diseases

Spleen cells, resting T cells, activated T cells, and T cell clones characterized as type 1 (Th1) and type 2 (Th2) were investigated for their ability to produce interferon (IFN) following in vitro culture with Newcastle disease virus (NDV). All of the above cell populations, including both Th1 and Th2 T cell clones, produced high levels of IFN following in vitro culture with NDV. This IFN was characterized as a mixture of IFN-alpha and IFN-beta with IFN-alpha being the predominate species of IFN contained in the mixture. IL-2 greatly enhanced the production of IFN-alpha/beta by all cell populations in response to NDV. These different T cell populations responded very differently to the immunoregulatory actions of IFN-gamma versus IFN-alpha/beta. IFN-alpha/beta was shown to be a potent inhibitor of Con A or IL-2-induced proliferation of different T cell populations. This inhibition was not associated with a reduction in lymphokine production since spleen cells or Th1 T cell clones cultured with Con A and IFN-alpha/beta had no decrease in IL-2 or IFN-gamma production when compared to Con A-stimulated control cultures. IFN-gamma had little to no inhibitory activity on Con A-induced proliferation of spleen cells. In fact, Con A-induced proliferation was usually enhanced by IFN-gamma when nylon wool-enriched T cells were assessed. Different results were observed when IFN-gamma and IFN-alpha/beta were investigated for their ability to inhibit IL-2-induced proliferation of different T helper cell clones. IFN-gamma and IFN-alpha/beta were both capable of inhibiting IL-2-induced proliferation of T cell clones characterized as type 2 (Th2). In contrast, IFN-gamma had no effect on IL-2-induced proliferation of Th1 clones. IFN-alpha/beta, however, inhibited IL-2-induced proliferative responses of both Th1 and Th2 T cell clones. These results document the facts that (1) IFN-gamma and IFN-alpha/beta differ in their immunoregulatory actions, (2) different T cell subpopulations vary in their susceptibility to IFN-gamma regulation, and (3) virus induction of IFN-alpha/beta appears to be a ubiquitous function associated with different T cell populations.

Topics: Animals; Cells, Cultured; Clone Cells; Concanavalin A; In Vitro Techniques; Interferon Type I; Interferon-gamma; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred C57BL; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Vesicular stomatitis Indiana virus; Virus Diseases

To better define the relationship between suppressor cell function and number and disease expression, the immunoregulatory profiles of 12 probands with systemic lupus erythematosus (SLE) and 34 of their asymptomatic family members were studied, using concanavalin A induced suppressor cells for functional analysis. SLE family members as a whole showed no impairment of mean suppressor levels, although 7 of 34 had altered suppression of DNA synthesis and 5 of 34 had altered suppression of IgG synthesis. Ratios of OKT4/T8 T cell subsets showed no difference between the study population, although 3 SLE family members had an increased ratio (greater than 2 SD) relative to controls. The 12 family members with either altered suppressor cell number or function had higher antibody levels to dRNA (Poly A . U) than did those with normal suppressor function and number. The results demonstrate that altered suppressor cell number and function occur in certain asymptomatic family members of SLE patients and may be weakly associated with markers of a preceding RNA viral infection.

Topics: Complement System Proteins; Concanavalin A; DNA; Female; Humans; Immunoglobulin G; Immunoglobulins; Lupus Erythematosus, Systemic; Male; Polynucleotides; T-Lymphocytes, Regulatory; Virus Diseases

Study of ecto-5'-nucleotidase was performed in cultured epithelial cells, infected with vesicular stomatitis virus (VSV). Changes in the enzymatic activity were measured in terms of TCID50 and exposure time. The effects of an enzyme inhibitor, Con A, were also investigated during the interaction between virus and cells.

Topics: 5'-Nucleotidase; Animals; Cattle; Cells, Cultured; Concanavalin A; Nucleotidases; Vesicular stomatitis Indiana virus; Virus Diseases

The in vitro increase in mitogenic potency of lysosome factors derived from peripheral blood granulocytes of patients with chronic viral myocarditis was observed. These factors inhibited in vitro the Con A-induced suppressor cell activity measured in lymphocytes from healthy persons. The obtained results suggested that these factors may cause disturbances in suppressor cell function in the course of the foregoing disease.

Topics: Adult; Cells, Cultured; Concanavalin A; Humans; Lymphocyte Activation; Middle Aged; Mitogens; Myocarditis; Neutrophils; T-Lymphocytes, Regulatory; Virus Diseases

The upper respiratory tract of 20 infants and children, suffering from viral diseases, have been investigated cytochemically and electron microscopically. We employed the electron microscope negative staining and the concanavalin-A-peroxidase methods in our investigations, besides the usual serological and immunological ones. Concanavalin-A-peroxidase reaction showed a characteristic damaging of the cell-surface which may play an important role in viral infection. The electron microscope negative staining investigations showed adeno-, herpes- and influenza-virions which are referring to viruses. These morphological methods are useful and they increase the efficiency of diagnosing viral infections.

Topics: Cell Membrane; Child; Child, Preschool; Concanavalin A; Histocytochemistry; Humans; Infant; Microscopy; Peroxidases; Respiratory System; Respiratory Tract Infections; Virus Diseases

Highly enriched populations of bovine neutrophils (PMN) were able to destroy herpesvirus-infected cells when in the presence of C. This mechanism of cytotoxicity was termed C-dependent neutrophil-mediated cytotoxicity (CDNC). To demonstrate CDNC required viable PMN, an active source of C, and a target cell expressing viral antigens. Noninfected cells were not susceptible to lysis. Several approaches were used to exclude the presence of antibody as an explanation for the cytotoxicity observed. In a comparison of the effectiveness of different cell types at mediating CDNC, PMN were more effective than macrophages, and lymphocytes were without activity. The results was discussed in terms of the possible in vivo significance of the neutrophil as a cell type capable of mediating recovery from infection, since if a mechanism similar to CDNC occurs in vivo, this could play a role in defense before the time when protective levels of antibody and immune cells are generated.

Topics: Animals; Antibody-Dependent Cell Cytotoxicity; Cattle; Cell Communication; Complement System Proteins; Concanavalin A; Cytotoxicity, Immunologic; Female; Herpesviridae Infections; Herpesvirus 1, Bovine; Infectious Bovine Rhinotracheitis; Kinetics; Neutrophils; Virus Diseases

Various polymorphonuclear leukocyte (PMN) functions are dependent on an intact intracellular cytoskeleton consisting of the microtubules and the microfilaments. To investigate the microtublule system in PMNs we observed the spontaneous, Colchicine and Diamide induced cap-formation by fluorescence microscopy ion PMNs obtained from children with bacterial and viral infections demonstrated with 47 +/- 1% a significantly increased number of spontaneous capped PMNs compared to 22 +/- 1% capped cells obtained from controls. Furthermore, 52 +/- 2% PMNs of patients on immunosuppressive therapy exhibited spontaneous surface capping. There was no significant elevation in the number of capped PMNs (30 +/- 2%) obtained from children with viral infections. Colchicine and Diamide increased the number of capped cells in control PMNs as well as in PMNs from patients to 69 +/- 1% and 67 +/- 1%, respectively. Since the increased spontaneous cap formation in PMNs is associated with a defect of microtubule assembly, the various leukocyte function defects described in patients with bacterial infections, bronchial asthma or on immunosuppressive therapy may have to be considered the consequence of an altered microtubule system.

Topics: Asthma; Bacterial Infections; Child; Colchicine; Concanavalin A; Cytoskeleton; Diamide; Humans; Immunosuppression Therapy; Leukocytes; Microtubules; Receptors, Concanavalin A; Virus Diseases

1. Serum samples were collected from ten patients hospitalized for acute infections and from a control group of seven normal subjects. Tissue ferritin was obtained by purification of ferritin from normal human liver and from the ferritin standard of a commercially available assay kit. 2. The serum and tissue samples were incubated with concanavalin A--Sepharose, which has the ability to bind normal serum ferritin. 3. Concanavalin A, a plant lectin which binds to glucose, can be coupled to Sepharose particles and by incubation and centrifugation ferritin in normal serum can be absorbed to about 70%. The serum and tissue samples were incubated with concanavalin A--Sepharose and the ferritin content was measured before and after. 4. It was found that ferritin in the serum of patients with acute infections was absorbed to the same extent as in normal serum (about 80%), irrespective of the initial value. Only about 20% of the tissue ferritin was absorbed. 5. It is concluded that the ferritin in serum during infection is of the same glucosylated type as the ferritin normally present in serum, whereas intracellular ferritin is not glycosylated. This indicates that the elevation of serum ferritin during infection is caused by a release along the normal pathways, i.e. an augmented synthesis, not by leakage from damaged cells.

Topics: Absorption; Adult; Bacterial Infections; Concanavalin A; Ferritins; Humans; Liver; Male; Sepharose; Virus Diseases

Topics: Animals; Cell Fusion; Cell Line; Cell-Free System; Concanavalin A; Cricetinae; Mice; Rabbits; Vesicular stomatitis Indiana virus; Virus Diseases

Spleen cells from nonlethally MCMV-infected weanling and adult DBA/2 mice had diminished responses to Con A stimulation. In contrast, only lethal MCMV infections were associated with a complete suppression of the Con A response. The immune response to SRBC was depressed even in asymptomatic infections of weanling and adult mice. A marked maturation of resistance to the lethal effects of MCMV infection was found to occur during the fourth week of life.

Topics: Age Factors; Animals; Antigens; Concanavalin A; Cytomegalovirus; Erythrocytes; Female; Injections, Intraperitoneal; Mice; Mice, Inbred DBA; Sheep; Spleen; T-Lymphocytes; Viral Plaque Assay; Virus Diseases

Topics: Agglutination; Agglutination Tests; Animals; Arboviruses; Cattle; Cell Line; Cell Membrane; Cells, Cultured; Chick Embryo; Concanavalin A; Cricetinae; Fibroblasts; HeLa Cells; Influenza A virus; Kidney; L Cells; Lectins; Newcastle disease virus; Orthomyxoviridae; Poliovirus; RNA Viruses; Semliki forest virus; Simian virus 40; Sindbis Virus; Vesicular stomatitis Indiana virus; Virus Diseases