concanavalin-a and Lung-Diseases

Depressed ADCC activity was found in sarcoidosis patients in clinical Stage II when whole blood was used as the effector cell pool. Whole blood in Stage I patients as well as purified peripheral lymphocytes of sarcoidosis patients did not reveal a diminished cytotoxic activity. Stimulation experiments with PHA, Con A, and PPD in two different concentrations resulted in a normal PHA response, a significantly decreased Con A response (regardless of the clinical stage of the patients), and a significantly decreased PPD responsiveness of peripheral lymphocytes in Stage II patients, respectively. Regarding the distribution of peripheral B and T lymphocytes, only a significantly depressed T-cell number in Stage I sarcoidosis patients was observed. Peripheral cells forming EA and EAC rosettes and staining for membrane-bound immunoglobulins were within normal ranges. Serum antibody titers to different herpes viruses, including Epstein-Barr virus, were found not to be elevated. Twenty percent of sarcoidosis patients showed anti-immunoglobulins in their sera specific for the Fc and Fab fragment.

Topics: Adult; Antibodies, Viral; Antigen-Antibody Reactions; B-Lymphocytes; Concanavalin A; Cytotoxicity Tests, Immunologic; Herpesviridae; Herpesvirus 4, Human; Humans; Immunoglobulin Fab Fragments; Immunoglobulin Fc Fragments; Lectins; Lung Diseases; Lymphocyte Activation; Sarcoidosis; T-Lymphocytes; Tuberculin

We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8(+) T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.

Topics: Angiotensin-Converting Enzyme 2; Animals; Brain Diseases; Cell Proliferation; Concanavalin A; Cytokines; Gene Expression Regulation, Enzymologic; Genetic Predisposition to Disease; Humans; Kinetics; Lung Diseases; Lymphocytes; Mice; Mice, Transgenic; Organ Specificity; Peptidyl-Dipeptidase A; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Spleen; Virus Replication

Given the role of cell-mediated immune responses in resistance to mycobacteria, we sought to analyse whether there was a relationship between the severity of pulmonary tuberculosis (TB) and lymphocyte proliferation as well as in vitro cytokine production. To achieve this, 25 untreated TB patients showing mild (n = 5), moderate (n = 9) or advanced (n = 11) pulmonary disease, and 12 age-matched healthy controls (mean+/-SD, 37+/-14.5 years) were studied. Peripheral blood mononuclear cells were cultured for 5 days with 10 microg/ml whole, sonicated Mycobacterium tuberculosis (WSA) or 2.5 microg/ml Concanavalin A (Con A). Supernatants were collected on day 4, from cultures grown with or without WSA, for measurement of interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-1beta and transforming growth factor-beta (TGF-beta). Antigen-specific proliferation was found to be reduced among patients and more profound in those with advanced disease who also displayed a depressed response to Con A. Patients with mild TB showed a preferential production of IFN-gamma over IL-4, gave the highest level of IFN-gamma synthesis upon specific antigen stimulation and showed increased levels of IL-1beta production. Findings in patients with moderate TB appeared compatible with a mixed production of IFN-gamma and IL-4 coexisting with a higher synthesis of TGF-beta, by comparison to patients with mild TB. Advanced disease showed the highest IL-4 and TGF-beta production, with IFN-gamma synthesis readily noticeable, yet decreased in comparison with the other patient groups. Differences in cytokine response according to the amount of lung involvement suggest a role for such mediators in the immunopathogenesis underlying the distinct clinical forms of pulmonary TB, that is a predominant T helper Th)1-like or Th2-like activity in mild or in progressive TB, respectively.

Topics: Adolescent; Adult; Aged; Antigens, Bacterial; Cells, Cultured; Concanavalin A; Female; Humans; Interferon-gamma; Interleukin-1; Interleukin-4; Leukocytes, Mononuclear; Lung Diseases; Lymphocyte Activation; Male; Middle Aged; Mycobacterium tuberculosis; Severity of Illness Index; Statistics, Nonparametric; T-Lymphocytes; Transforming Growth Factor beta; Tuberculosis

In vitro and in vivo T cell responses were determined during the course of bronchopulmonary infection with mucoid Pseudomonas aeruginosa. T cell responses were compared in two inbred mouse strains, namely BALB/c mice, which are resistant to the establishment of chronic bronchopulmonary Ps. aeruginosa infection, and C57Bl/6 mice, which have high numbers of bacteria in the lungs through 14 days post-infection. Unseparated lung cells and lung T cells from BALB/c mice exhibited significantly higher in vitro proliferative responses to both heat-killed Ps. aeruginosa and concanavalin A (Con A) than cells from C57Bl/6 mice through 20 days post-intratracheal infection with 10(4) colony-forming units (CFU) Ps. aeruginosa. Proliferation of unseparated lung cells but not lung T cells from BALB/c mice infected 6 days previously with 10(5) CFU Ps. aeruginosa was suppressed in response to Con A; these cells were unresponsive to specific antigen. Suppression of lymphocyte proliferation in the lungs of C57Bl/6 mice infected with 10(4) CFU Ps. aeruginosa and in BALB/c mice infected with 10(5) CFU was found to be mediated by adherent lung cells via the production of nitric oxide and prostaglandins. Determination of in vivo T cell-mediated responses in infected mice demonstrated that resistant BALB/c mice had high DTH and low Pseudomonas-specific antibody responses, while C57Bl/6 mice had low DTH and high antibody levels, in particular, IgG2b and IgM.

Topics: Animals; Antibodies, Bacterial; Bronchial Diseases; Cell Division; Cells, Cultured; Chronic Disease; Concanavalin A; Disease Models, Animal; Female; Hypersensitivity, Delayed; Immunity, Cellular; Lung; Lung Diseases; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pseudomonas Infections; T-Lymphocytes

Lung macrophages may play an important role in the pathogenesis of pulmonary sarcoidosis. In this study, the ability of pulmonary macrophages and blood monocytes from sarcoidosis patients, normal controls and disease controls to provide the accessory signal necessary for the concanavalin A-induced activation of normal blood T cells was examined. Blood monocytes from all groups supplied a significantly greater accessory signal than lung macrophages. The accessory capacity of lavage macrophages from sarcoidosis patients varied over a wide range and correlations were sought between these values and other parameters of disease activity. Whilst there was no correlation with clinical parameters, accessory function of alveolar macrophages correlated significantly with the percentage of T helper cells in bronchoalveolar lavage (BAL) fluid (p less than 0.05) and, more closely, with the T helper:T suppressor ratio in BAL fluid (p less than 0.01). This interrelationship between macrophage activity and the T cell infiltrate favours the probability that both cell types participate in the sarcoid disease process and raises the possibility that T cells of both helper and suppressor phenotypes contribute to the pathogenesis.

Topics: Adult; Aged; Antigen-Presenting Cells; Bronchoalveolar Lavage Fluid; Concanavalin A; Female; Humans; Lung Diseases; Lymphocyte Activation; Macrophages; Male; Middle Aged; Monocytes; Pulmonary Alveoli; Pulmonary Fibrosis; Sarcoidosis; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

A model of acute immunological lung injury, initiated by the binding of passively administered antibody to an antigen (Concanavalin A (Con A] affixed to the pulmonary endothelium, is described. Pulmonary injury, monitored using the 125I-albumin lung permeability index (LPI) did not occur with antigen deposition alone (LPI 0.235 +/- 0.012). The binding of antibody to the 'planted' lung antigen resulted in injury only when antibody binding exceeded a threshold value of 7.4 +/- 1.4 micrograms antibody globulin per gram of lung. Alevolar-capillary permeability changes were maximal 4 to 8 h after antigen-antibody interaction (LPI at 2 h, 0.353 +/- 0.015: at 4 h, 0.387 +0.33; at 8 h, 0.373 +/- 0.025; at 24 h, 0.289 +/- 0.031; at 48 h, 0.239 +/- 0.022). Lung injury was significantly attenuated by neutrophil (PMN) depletion (LPI at 4 h, 0.325 +/- 0.014: P less than 0.01cf PMN-intact animals), and further reduced by complement depletion (LPI at 4 h, 0.275 +/- 0.023: P less than 0.05 cf PMN-intact and PMN-deplete animals). This model of immune lung injury demonstrates the potential for in situ immune reactions on the pulmonary endothelial surface to induce acute inflammatory injury. Further the model illustrates the cooperative effects of neutrophils and complement in the genesis of inflammation, with both these mediator systems contributing to immunological pulmonary injury.

Topics: Acute Disease; Animals; Complement System Proteins; Concanavalin A; Disease Models, Animal; Immune Complex Diseases; Lung; Lung Diseases; Male; Neutrophils; Rats; Rats, Inbred Strains

BAL and blood mononuclear cells and their reactivity to Kveim antigen, tuberculin and concanavalin A (Con A) were studied in nine patients with different clinical stages of sarcoidosis. After separation by plastic adherence, non-adherent cells (mainly lymphocytes) were admixed with 10% autologous adherent cells (monocytes/macrophages). After 3 and 6 days' culture with Kveim antigen (1, 10, 100 micrograms/ml), PPD tuberculin (2.5 micrograms/ml) and Con A (10, 20, 40 micrograms/ml) stimulation was measured as incorporation of 14C-thymidine into DNA. Except for occasional reactions the study did not show any unitary significant increase in lymphocyte response to the different concentrations of Kveim antigen in either BAL or blood. For Con A there was a weaker response by BAL-mononuclear cells with no difference between 3 and 6 days, compared with blood where there was an early peak. The lymphocyte reaction to PPD was weak with no difference between blood and BAL.

Topics: Adult; Bronchoalveolar Lavage Fluid; Concanavalin A; Female; Humans; Kveim Test; Leukocyte Count; Lung Diseases; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Sarcoidosis; Skin Tests; Stimulation, Chemical; Tuberculin

Granuloma formation in the lung of patients with sarcoidosis is preceded by the accumulation of large numbers of activated T-lymphocytes, which results, at least in part, from the proliferation of T-lymphocytes within the lung. To determine whether the increased proliferation of lung T-lymphocytes in sarcoidosis results from a failure of mechanisms responsible for limiting their proliferation, we have compared the ability of purified T-lymphocytes present in bronchoalveolar lavage fluid and peripheral blood from normal subjects and patients with sarcoidosis to respond to proliferative signals. The mitogen-induced proliferative response of lavage T-lymphocytes from normal subjects and patients with sarcoidosis was similar, but the response of lavage T-lymphocytes was much less than that observed using normal or sarcoid blood T-lymphocytes. The reduced proliferative response of sarcoid lavage T-lymphocytes could not be overcome by addition of accessory cells or exogenous interleukin-2, and it did not result from the presence of suppressor cells. Furthermore, sarcoid lavage lymphocytes are capable of being activated by "mitogenic" signals, as indicated by the ability of phytohemagglutinin to induce expression of the 4F2 surface antigen and stimulate interleukin-2 production. However, the expression of interleukin-2 receptors was reduced on stimulated sarcoid lavage T-lymphocytes compared with that observed on normal blood T-lymphocytes, which may account in part for their reduced proliferative capacity. Because mechanisms that render lavage T-lymphocytes from normal subjects refractory to proliferative signals appear to operate in sarcoidosis as well, these findings suggest that a defect in the inhibition of T-lymphocyte proliferation is unlikely to be an important cause of lymphocyte accumulation in this disorder.

Topics: Adult; Bronchoalveolar Lavage Fluid; Cell Division; Concanavalin A; Female; Humans; Interleukin-2; Lung Diseases; Major Histocompatibility Complex; Male; Phytohemagglutinins; Receptors, Antigen; Sarcoidosis; T-Lymphocytes

Patients with nonthyroid illness (NTI) often have reduced serum T3, free T3, T4, and free T4 concentrations. Paradoxically, serum TSH is usually in the normal range. The data suggest a diagnosis of hypothalamic hypothyroidism, in which TSH may have reduced biological activity because TRH, which is necessary for key steps in the glycosylation of TSH, is deficient. To study the glycosylation of TSH in patients with NTI, we measured the serum TSH concentration in 36 such patients hospitalized on our intensive care units and compared the results with those from a group of 18 normal subjects. Serum TSH was measured in 2 assays: 1) a sensitive TSH RIA of unextracted serum (TSH-RIA) and 2) a RIA of serum TSH after its extraction with Concanavalin-A (Con-A), a lectin which binds glycoproteins containing mannose residues in their oligosaccharide side-chains (TSH-Con-A). The ratio of TSH-Con-A to TSH-RIA was significantly reduced in the NTI patients [0.61 +/- 0.03 (+/- SE) vs. 0.89 +/- 0.05 in the normal subjects] due to reduced binding of the TSH to the Con-A. This change was not dependent on the extent of the abnormalities of thyroid hormone levels. The data suggest that the TSH secreted in NTI has altered glycosylation which is associated with reduced biological activity. This finding may explain in part the low serum T4 level in NTI patients in the face of an apparently normal immunoreactive TSH level.

Topics: Adult; Aged; Concanavalin A; Heart Diseases; Humans; Lung Diseases; Middle Aged; Protein Binding; Radioimmunoassay; Thyroid Diseases; Thyroid Hormones; Thyrotropin; Thyroxine

Topics: Animals; Cell Movement; Cell Separation; Cells, Cultured; Concanavalin A; Histamine; Humans; Lung; Lung Diseases; Lymphokines; Monocytes; Rats; Sarcoidosis; T-Lymphocytes, Helper-Inducer

We have reported previously that pulmonary alveolar macrophages (PAMs) from individuals with lung cancer and active chronic pulmonary diseases were cytotoxic to tumor cells in vitro, whereas PAMs from normal individuals or patients with acute pulmonary disorders were noncytotoxic. In the present study, we evaluated 20 PAM preparations for both suppressor and cytotoxic functions to determine if PAMs could function as suppressor cells and, if so, whether a correlation between the two functions exists. Cytotoxicity was assessed in a 60-hr cytotoxicity assay against [3H]proline-prelabeled human melanoma target cells. More than 20% cytotoxicity was considered to be significant. Suppressor activity was measured by determining whether admixing PAMs at various ratios with autologous or allogeneic mononuclear cells could suppress concanavalin A-induced blastogenesis by T-lymphocytes. At least 50% suppression was considered to be significant. Of the 20 specimens evaluated, 13 were cytotoxic and 5 of these exhibited suppressor activity. None of the 7 noncytotoxic PAM preparations had suppressor activity. Suppression was nonspecific and not HLA restricted, since autologous and allogeneic mononuclear cells were inhibited to a similar extent. Suppression was probably not due to prostaglandin production by the PAMs since assays were performed under optimal conditions and required extremely high concentrations of prostaglandins. A significant correlation between suppressor and cytotoxic activity was found. Suppression was observed only with PAM specimens that were also highly cytotoxic to tumors, but not all cytotoxic PAM specimens were suppressive. Whether these actions reflect different levels of activation of PAMs or are the properties of different macrophage subsets remains to be clarified.

Topics: Concanavalin A; Cytotoxicity, Immunologic; DNA Replication; Humans; Immune Tolerance; Lung; Lung Diseases; Lymphocyte Activation; Macrophages; Melanoma; Monocytes; T-Lymphocytes

We have shown that peripheral blood monocytes from patients with sarcoidosis release reduced amounts of interleukin-1 (IL-1) when compared with normals. In part, this defect explains the relative in vitro unresponsiveness of T lymphocytes from patients with sarcoidosis as measured by mitogen- or antigen-induced lymphocyte transformation. The addition of supernatants containing pre-formed IL-1 partially restored this defect. This enhancement was found to be additive to the previously described effect of indomethacin, an inhibitor of prostaglandin synthesis. Thus, it would appear that the activated peripheral blood monocytes found in sarcoidosis not only cause reduced lymphocyte proliferation by acting as suppressor cells but are also unable to act as accessory cells in producing IL-1.

Topics: Adult; Aged; Concanavalin A; Dinoprostone; Female; Humans; Indomethacin; Interleukin-1; Lipopolysaccharides; Lung Diseases; Lymphocyte Activation; Male; Middle Aged; Monocytes; Prostaglandins E; Sarcoidosis; T-Lymphocytes

The concentration of alpha 1-acid glycoprotein (AGP, orosomucoid) was measured in sera from 19 patients with primary squamous cell carcinoma of the lung, 16 patients with an inflammatory lung disease and 17 persons with normal health. All sera were further subjected to crossed immuno-affinoelectrophoresis with addition of Con A in the first dimension and sugar in the second dimension. The distribution of AGP into four microheterogeneity forms, which were the result of this analysis, was estimated by measuring the area under the precipitation curve. The microheterogeneity patterns of AGP in the three groups were significantly different from each other (p less than 0.001). The total concentration of AGP in the two groups of patients was significantly different from the concentration in the healthy group (p less than 0.001).

Topics: Carcinoma, Squamous Cell; Concanavalin A; Humans; Immunoelectrophoresis, Two-Dimensional; Lung Diseases; Lung Neoplasms; Orosomucoid

Topics: Adult; alpha-Macroglobulins; Concanavalin A; Cystic Fibrosis; Heterozygote; Humans; Immunoglobulin G; Immunoglobulin M; Lung Diseases; Protein Binding

The lung, by virtue of its anatomic situation, provides environmental antigens with unique access to host lymphoid tissues. In order to better understand the biologic consequences of antigen inhalation, we developed in animal model in which soluble proteins are administered in aerosol form to rabbits. By labeling these proteins with fluorochrome dyes or radioactive isotopes, the uptake, distribution, and fate of such proteins can be demonstrated both morphologically and quantitatively. Prompt host-antibody responses can be demonstrated to inhaled antigen, but not to comparable amounts of ingested antigen. Repeated administrations of antigen aerosol to immune animals produced little injury; in contrast, administration of aerosols containing phytohemagglutinin or cancanavalin A (Con A), plant lectins which activate leucocytes in a polyclonal fashion, induced a diffuse interstitial pneumonitis. When immune animals inhaled antigen plus Con A, devastating pulmonary necrosis was induced, in association with localized deposits of immune complexes containing antigen, antibody and complement. Such necrotic injury healed by scarring within 4 weeks. The necrotizing injury could be prevented by either decomplementation with cobra venom factor, or through inhibition of leucocyte responsiveness to Con A by administration of cholera toxin, a cAMP agonist. These studies indicate that antigen inhalation may serve as an important means of establishing "natural" immunity to environmental agents, but also may lead to severe pulmonary injury and fibrosis where the agents inhaled act not only as antigens but as polyclonal leucocyte activators as well.

Topics: Aerosols; Animals; Antigens; Arthus Reaction; Cholera Toxin; Concanavalin A; Cyclic AMP; Cyclic GMP; Disease Models, Animal; Hypersensitivity, Delayed; Immune Complex Diseases; Lung; Lung Diseases; Lymphocyte Activation; Male; Rabbits; Respiratory Hypersensitivity; Serum Albumin, Bovine; Skin Tests

Some in vitro functions of purified T and B cells from PPD- and Candida albicans-negative sarcoidosis patients were analyzed. It appears that in those patients there is: 1) A decrease in the absolute number of T lymphocytes and an increase in the number of B cells; 2) a rather normal response of T lymphocytes to PHA and Con A; 3) a rather normal capacity of T and B cells to produce MIF in vitro; and 4) an ability of T cells from sarcoid patients (but not B cells) to produce LMF. These results suggest that the frequent deficit in cell-mediated immunity observed in sarcoidosis seems to correlate with a quantitative deficit in T cells. The cause of this T-cell deficit is unknown.

Topics: Adolescent; Adult; B-Lymphocytes; Candida albicans; Concanavalin A; Humans; Immunity, Cellular; Lectins; Lung Diseases; Lymphocyte Activation; Lymphokines; Macrophage Migration-Inhibitory Factors; Middle Aged; Sarcoidosis; T-Lymphocytes; Tuberculin Test

Peripheral blood lymphocytes of nine patients with pulmonary sarcoidosis were collected before and after a standardized bicycle ergometer test. The lymphocytes were characterized by various cell surface markers as T or B lymphocytes, and functionally by mitogen- or antigen-induced DNA synthesis and by antibody dependent cell-mediated cytotoxicity. Physical work resulted in an increase of circulating lymphocytes. Proportionately more B lymphocytes were mobilized. The DNA synthesis of lymphocytes in response to mitogens and antigen was reduced, whereas the cytotoxicity was augmented. Compared with normals the mobilization of lymphocytes was less, and a deficiency of both T and B lymphocytes was revealed. The functional impairment of lymphocytes in the patient group persisted.

Topics: Adult; B-Lymphocytes; Concanavalin A; Cytotoxicity Tests, Immunologic; DNA; Humans; Lectins; Lung Diseases; Lymphocyte Activation; Male; Physical Exertion; Sarcoidosis; T-Lymphocytes