concanavalin-a and Bacterial-Infections

Topics: Bacteria; Bacterial Infections; Biosensing Techniques; Concanavalin A; Enterococcus faecalis; Escherichia coli; Humans; Lectins; Limit of Detection; Monosaccharides; Nanotubes, Carbon; Principal Component Analysis; Streptococcus mutans

Studies have indicated that a shift from a Th1 to a Th2 response occurs that contributes to the late immunosuppression seen during sepsis. However, the mechanism by which this occurs is unknown. In this regard, mediators released in response to sepsis are thought to upregulate a family of stress-induced mitogen-activated protein kinases (MAPKs), such as JNK, ERK, and p38 MAPK, which may play a role in this process.. To determine the role of MAPK in immune suppression, we induced polymicrobial sepsis in C3H/HeN male mice using cecal ligation and puncture (CLP). Splenic lymphocytes were harvested 24 h post-CLP and stimulated with the T-cell mitogen concanavalin A, and the expression and activation of these MAPKs were assessed by Western analysis. To determine the extent to which these MAPKs may have an impact on splenic immune function, cells were pretreated with a 10 microM concentration of the p38 MAPK inhibitor SB203580 or the MEK inhibitor PD98059 or with DMSO vehicle. The cells were then stimulated with 2.5 microg/ml of the T-cell mitogen concanavalin A, and cytokine release was then determined (by ELISA).. In the lymphocytes from CLP mice no JNK signal was detected, however, p38 expression and activation were markedly (P < 0.05, n = 6) increased. In contrast, the expression of activated ERK markedly decreased following septic challenge. The results indicate that p38 MAPK inhibition with SB203580 suppressed the sepsis-induced augmentation of interleukin-10 release while restoring the suppressed Th1 cytokine interleukin-2 release typically encountered following sepsis. Inhibition of ERK had no effect on cytokine release. Neither PD98059 nor SB203580 had an effect on interferon gamma release or on proliferative capacity.. This would indicate that the induction of p38 MAPK activation in splenocytes contributes to the immunosuppression seen in late sepsis.

Topics: Animals; Bacterial Infections; Cell Division; Concanavalin A; Enzyme Activation; Enzyme Inhibitors; Flavonoids; Imidazoles; Immune Tolerance; Interferon-gamma; Interleukin-10; Interleukin-2; Male; Mice; Mice, Inbred C3H; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Pyridines; Spleen; Th1 Cells; Th2 Cells

Agarose based affinity immunoelectrophoresis with free concanavalin A (Con-A) as ligand was used to examine the microheterogeneity of alpha 1-acid glycoprotein in sera of patients with systemic onset juvenile rheumatoid arthritis (JRA) and acute bacterial infections. In JRA, a decreased proportion of Con-A reactive alpha 1-acid glycoprotein variants was found when compared to healthy control. In contrast, acute bacterial infection showed an increased reactivity. Investigation of glycosylation may be useful in the differential diagnosis of systemic onset JRA and acute bacterial infection.

Topics: Acute Disease; Arthritis, Juvenile; Bacterial Infections; C-Reactive Protein; Child; Child, Preschool; Concanavalin A; Diagnosis, Differential; Glycosylation; Humans; Immunoelectrophoresis; Ligands; Orosomucoid

A murine model of experimental sepsis, ie, cecal ligation and puncture, was used to determine the potential effects of infection on in vitro cell-mediated immunity. Following cecal ligation and puncture, in vitro responses of mouse splenocytes to mitogens (phytohemagglutinin and concanavalin A), the effects of in vitro interleukin 2 on these responses, and the impact of in vivo interleukin 2 on survival were studied. Compared with controls (sham cecal ligation and puncture), phytohemagglutinin responses 1 day after cecal ligation and puncture were enhanced (43% +/- 17%, n = 9), phytohemagglutinin and concanavalin A responses at day 4 were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%), and, by day 7, phytohemagglutinin and concanavalin A responses were approaching values in mice treated by sham cecal ligation and puncture. Suppressed phytohemagglutinin responses at day 4 after cecal ligation and puncture were restored to normal with in vitro interleukin 2 (61,052 +/- 3407 cpm for cecal ligation and puncture and 64,643 +/- 4727 cpm for sham cecal ligation and puncture). Mortalities following cecal ligation and puncture were identical at day 1 after cecal ligation and puncture (6/20) for both interleukin 2- and vehicle-treated groups; thereafter, interleukin 2-treated groups fared better. At day 1 after cecal ligation and puncture, the mean spleen cell phytohemagglutinin response was enhanced (43.8% +/- 17%, n = 9) compared with sham cecal ligation and puncture (= 10). By day 4, the responses to both concanavalin A and phytohemagglutinin were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%, respectively). Responses at day 7 approached those of controls given sham cecal ligation and puncture. Sepsis causing a temporary impairment of cell-mediated immunity may be a factor in the frequent coexistence of altered cell-mediated immunity and sepsis, and interleukin 2 may have a role in limiting the adverse effects of sepsis.

Topics: Abdomen; Animals; Bacterial Infections; Concanavalin A; Disease Models, Animal; Drug Evaluation; Humans; Immunity, Cellular; Interleukin-2; Male; Mice; Mice, Inbred A; Phytohemagglutinins; Recombinant Proteins; Time Factors

Microheterogeneity of acute phase proteins frequently differs in acute and chronic types of inflammation. However, it is unknown whether these changes depend on the duration of the inflammation in a given disease. We therefore investigated the microheterogeneity of alpha 1-acid glycoprotein (AGP) in sera from patients with acute and chronic bacterial infection in comparison to rheumatoid arthritis and ankylosing spondylitis. In acute bacterial infection Con A-reactivity of AGP was significantly elevated. By contrast, AGP in chronic bacterial infection showed the same glycosylation pattern as rheumatoid arthritis and ankylosing spondylitis being characterized by a decreased reactivity to Con A. Serial measurements in individual patients with bacterial infections showed a transition from the initially elevated to decreased reactivity to Con A as the disease became chronic.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Bacterial Infections; C-Reactive Protein; Chronic Disease; Concanavalin A; Female; Glycosylation; Humans; Immunoelectrophoresis, Two-Dimensional; Male; Middle Aged; Orosomucoid; Spondylitis, Ankylosing; Staphylococcal Infections; Streptococcal Infections

Iron is an essential growth factor for procaryotes as well as for eucaryotes. Microorganisms have developed specific iron-uptake systems by producing low-molecular weight iron-chelating compounds (siderophores). We have examined the effect of the siderophores desferrioxamine (DFO), desferrichrome (DFC), desferriaerobactin (DFAB) and desferrienterobactin (DFEA) on the mitogen-stimulated activation and proliferation of mouse T cells. The hydroxamate siderophores DFO, DFC and DFAB cause an immunosuppressive effect on T cells which is related to the iron complexation constant of the siderophores and can be reversed by equimolar ferric iron. In contrast, the catecholate siderophore DFEB and its ferrated derivative turned out to be cytotoxic for T cells. These results suggest a dual role of siderophores in the infectious process, i.e., growth enhancement of the invading pathogen and inhibition of the host immune defense.

Topics: Animals; Bacterial Infections; Chelating Agents; Concanavalin A; Female; Immune Tolerance; Ionophores; Iron; Iron Chelating Agents; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Receptors, Interleukin-2; Siderophores; T-Lymphocytes

We evaluated the clinical usefulness of determinations of alpha 1-acid glycoprotein (AGP) microheterogeneity in distinguishing patients who have active rheumatoid arthritis (RA) from those who have RA and an intercurrent infection. AGP microheterogeneity was studied by affinity electrophoresis with concanavalin A as the ligand, and the results were expressed as reactivity coefficients (RC). Significant differences were found between the mean RC (+/- SD) in healthy individuals (1.27 +/- 0.16) and the mean RC in RA patients with intercurrent infection (1.74 +/- 0.90), as well as with the mean RC in RA patients with grades III and IV disease activity (0.92 +/- 0.18 and 0.81 +/- 0.25, respectively). Moreover, an additional microheterogeneous form of AGP, similar to that observed in non-RA patients with infections, was noted in RA patients with infections (sensitivity 100%, specificity 100%). The results show that an increase in AGP reactivity with concanavalin A is a sensitive indicator of intercurrent infection in patients with RA.

Topics: Arthritis, Rheumatoid; Bacterial Infections; C-Reactive Protein; Concanavalin A; Electrophoresis, Gel, Two-Dimensional; Humans; Orosomucoid

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

The high morbidity after severe thermal insult is believed to be related partially to a resultant decrease in immunocompetence. We tested the ability of phytohemagglutinin (PHA) and Concanavalin (Con A) to stimulate lymphocyte transformation in 17 patients with moderate to severe thermal injury (greater than 25% BSA). The patients acted as their own controls and the per cent change in their mitogen response was measured over time. Eight acutely burned patients who subsequently developed severe sepsis (Group I) had decreased ability (mean, 12% of normal) to proliferate in response to PHA, and six of these died of severe sepsis. The depressed response appeared 4 to 7 days postinjury and predated clinical evidence of sepsis by 2 to 4 days. Cells from four patients who had mild infectious complications (Group II) demonstrated greatly augmented mitogen responses (mean + 243%) approximately 7 to 10 days postinjury. Five burn patients whose clinical course was sepsis free (Group III) exhibited only minimal changes in their mitogen responses (mean +30%). Although the Con A responses of the patients' cells corresponded less to their pathology, Group I patients whose cells exhibited depressed PHA responsiveness also had diminished Con A responses. Group II patients' cells also showed increases in Con A-induced stimulation. Group III patients, who had only slightly augmented PHA responses, had minimal decreases of the Con A-induced lymphocyte transformation. Many severely burned patients develop septicemia as a result of their large wound surfaces. The appearance of decreases in mitogen-induced proliferation, however, appears to characterize those patients who will be unable to handle the septic challenge.

Topics: Adult; Aged; Bacterial Infections; Burns; Concanavalin A; Escherichia coli Infections; Female; Humans; Immunocompetence; Klebsiella Infections; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Prognosis; Pseudomonas Infections; Sepsis; Staphylococcal Infections; T-Lymphocytes; Time Factors

Topics: Animals; Antilymphocyte Serum; Azathioprine; B-Lymphocytes; Bacterial Infections; Concanavalin A; Dermatitis, Atopic; Graft Rejection; Hodgkin Disease; Humans; Immunosuppressive Agents; Kidney Transplantation; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Prednisone; Rabbits; Renal Dialysis; Sarcoidosis; T-Lymphocytes; Transplantation, Homologous