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Biomedical subjects

M Suko

Publications and source records attributed to M Suko.

At least 91 records · Page 5Linked to original sources

Monocyte activating factor in sarcoidosis. II. Secretion of the factor from monocytes.

The normal human monocytes pretreated with the monocyte activating factor found in sarcoidosis sera were shown to secrete a factor which induced normal human monocytes to spread as well as to increase their cell size. Phagocytosis and glucose consumption of normal human monocytes were also increased by this secondarily obtained factor. Its molecular weight was about 70,000. These results indicate that this secondary factor may be the same substance as the monocyte activating factor found in sarcoidosis sera. The normal human monocytes pretreated with the monocyte activating factor were also shown to liberate a factor which generated macrophage migration inhibitory factor in cooperation with normal human sera.

Animals↗

IgG2 antibodies block IgE antibody-induced asthma in guinea pigs.

In order to examine the blocking activity of IgG2 antibodies to guinea pig for IgE antibodies-induced guinea pig asthma, experiments were carried out as follows. Guinea pigs were passively sensitized intravenously with guinea pig serum containing IgE antibodies to ovalbumin (OA). 8 days after sensitization, IgG2 purified from guinea pigs hyperimmunized with OA was intravenously injected. One hour later, the guinea pigs were challenged by inhalation of OA solution. Asthma attacks were not observed in the guinea pigs, whereas the attacks were observed in guinea pigs passively sensitized with the IgE antibodies but injected IgG2 fraction from normal guinea pigs 1 h before inhalation. These observations suggested that IgG antibodies that increased after immunotherapy might block asthma caused by inhalation of allergens in humans.

Animals↗

Granulomatous pneumonitis induced by bacille Calmette-Guérin in the mouse and its treatment with cyclosporin A.

Granulomatous pneumonitis was induced intravenously by an injection of BCG, and changes in the population of cells from bronchoalveolar lavage (BAL) fluid were examined. Increased lymphocytes in BAL fluid, especially Lyt-1 positive T-lymphocytes, were observed after the development of granulomatous pneumonitis. Cyclosporin A (Cy A) administered for 5 days before and for 5 days after BCG injection clearly suppressed development of the granuloma. The BAL cell count and cell population became almost the same as those in naive animals. The increase in the number of Lyt-1 positive T cells was abrogated by Cy A treatment. These results suggested the important role of Lyt-1 positive T cells in the development of granulomas and the possible beneficial effect of Cy A in human granulomatous lung diseases.

Animals↗

Desensitization. V: Suppression of MIF production by lymphokine-activated macrophages.

The systemic injection of high doses of antigen into a previously immunized animal results in a state of transient anergy with respect to cell-mediated immune reactions. This phenomenon is known as desensitization. We have previously shown that desensitization is a multistage process. The initial 24-hr period is characterized by excessive lymphokine production with a failure to express delayed hypersensitivity reactions due to abolition of local chemotactic gradients. Subsequent stages of desensitization involve failure of lymphokine production in vivo. The results presented here demonstrate that lymphocytes obtained from immunized and desensitized animals later than 24 hr after desensitization are markedly suppressed in their ability to produce MIF. In addition, it was found that lymphokine-activated macrophages can suppress in vitro MIF production by lymphocytes from immune, nondesensitized animals. In vitro and in vivo activation of macrophages were equally effective. Thus, it is likely that at least one mechanism for the inhibition of lymphokine production in the post-24-hr period of desensitization, involves activation of a population of suppressor macrophages by lymphokines produced during the initial 24-hr period.

Animals↗

Cellular hypersensitivity to human pancreatic B-cell clone in diabetes mellitus and its relationship to the presence of islet cell antibodies.

A leukocyte migration inhibition test on the human pancreatic B-cell clone (JHPI-1) was performed in 13 IDDM patients with islet cell cytoplasmic antibody (ICCA) and/or islet cell surface antibody (ICSA), 15 IDDM patients without ICCA or ICSA, 34 NIDDM patients and 17 healthy controls. The mean values for the migration index (M.I. %) in each group were 85.4 +/- 6.9, 89.1 +/- 10.9, 98.3 +/- 7.9 and 100.0 +/- 8.5. The M.I. values were significantly decreased in IDDM patients than in NIDDM patients and controls irrespective of whether or not there were islet cell antibodies in the patients' sera. When M.I. values less than 0.83 (Mean-2 S.D.) were taken as indicative of inhibition, the percentage of IDDM and NIDDM patients with migration inhibition were 32% and 0% respectively. And the decreased M.I. values in IDDM patients proved not to be due to non-specific migration inhibition by normal M.I. values, with the human fetal lung fibroblast cells (W 138) as antigen. Our data suggested that the lymphocytes of IDDM patients might be sensitized by pancreatic B-cell antigen(s) present in the JHPI-1 cells, which promoted leukocyte migration inhibition. No correlation between the migration indices and duration of diabetes mellitus in IDDM patients was observed (r = 0.254, Y = 84.9 + 0.49 X). LMT to JHPI-1 seems to be useful in detecting the abnormal cell-mediated immunity even in patients with longstanding IDDM.

Adolescent↗

Decreased airway responsiveness to histamine in gold salt-treated guinea pigs.

The effect of gold salts on airway responsiveness was examined because gold salts appear to be effective in relieving asthmatic symptoms. Seventeen guinea pigs were administered an intramuscular injection of 1 mg of gold sodium thiomalate once a week, and 10 control animals were administered an injection of saline. Three months after the start of the injections, guinea pigs administered gold salt demonstrated significantly decreased airway responsiveness to histamine assessed by respiratory flow patterns and resistance. Some guinea pigs in each group were sacrificed 3 mo after the start of injections, and cyclic nucleotides were measured in the trachea, lung homogenates, and the plasma. No difference was found in the level of adenosine cyclic 3', 5'-monophosphate or guanosine cyclic 3',5' -monophosphate in gold salt-treated animals and control animals. The way in which gold salt alleviates the symptoms of bronchial asthma is discussed on the basis of the results.

Airway Resistance↗

Contraction of guinea pig trachea with antibodies to guinea pig IgE. An in vitro model for asthma. II. Reactivity of guinea pig tracheas to anti IgG1 and anti IgG2 in comparison with anti IgE.

Although relatively small quantities of antibody to guinea pig IgE were shown to contract isolated guinea pig trachea in vitro, relatively large quantities of anti IgG1 were required to elicit similar responses. Under similar conditions, anti IgG2 did not provoke contraction. Following intravenous injection of these antisera into normal guinea pigs, anaphylaxis or asthma could be only provoked by anti IgE.

Animals↗

IgE levels in nude mice.

IgE levels in nude mice were estimated by the one-step single radial radiodiffusion method antisera prepared by immunization of guinea pigs with an IgE-rich fraction obtained from sera of normal mice infected with Nippostrongylus brasiliensis and immunized with DNP-ovalbumin in alum gel. 3 out of 8 nude mice had IgE levels significantly higher than those of normal mice.

Animals↗

Antibody formation to double-stranded DNA in nu/nu and nu/+ mice.

Antibody formation to double-stranded (ds-) DNA in nude mice (nu/nu) and normal littermates (nu/+) was studied using a Millipore filter method. The mean antibody titre to ds-DNA in the sera of nu/nu mice was generally higher than that in nu/+ mice raised in the same environment. However, in both genotypes, anti-ds-DNA titres varied according to the environmental condition in which the animals were raised. Mice maintained germ-free showed no significant antibody formation to ds-DNA. Nu/+ thymus and spleen cells passively transferred to nu/nu mice reduced the antibody titre to ds-DNA in the recipients. Immunochemical studies indicated that the antibodies to ds-DNA were IgM. It is suggested that T cell-mediated regulatory mechanisms control antibody formation to ds-DNA and that some infections trigger antibody formation to ds-DNA.

Animals↗

Preferential enhancement of IgE antibody formation by Bordetella pertussis.

Preferential enhancement of IgE antibody response was observed in BALF/c mice by the administration of Bordetella pertussis with antigen (DNP-Salmonella). Correlation between B cell mitogenic activity and adjuvant action among B. pertussis, Salmonella, lipopolysaccharide of Escherichia coli and Ficoll was examined but was not found. Thymus-derived cells seemed necessary to develop adjuvant action of B. pertussis since antibody response in athymic nude mice was not influenced by B. pertussis. Helper function of adoptively transfered spleen cells was enhanced by immunization of the donor mice with carrier antigen in the presence of B. pertussis. The magnitude of enhancement was greatest in IgE class. The results indicated that preferential enhancement of IgE antibody formation by B. pertussis is mediated by the augmentation of carrier-specific helper function.

Adjuvants, Immunologic↗

Allergen-specific human T cell clones produce interleukin-5 upon stimulation with the Th1 cytokine interleukin-2.

CD4+ T cell clones specific for Der fII (a major allergen of the house dust mite) were established from peripheral blood mononuclear cells of atopic patients. All of the T cell clones were classified as having the Th0 phenotype, since they produced both interleukin (IL)-2 and IL-4 upon stimulation. Some of the clones produced IL-5 upon antigenic stimulation. Human recombinant IL-2 induced these T cell clones to express IL-5 mRNA and produce IL-5 protein in a dose-dependent manner. IL-2 did not induce IL-4 production, indicating a discrete signal requirement for IL-4 versus IL-5 production by T cells. Moreover, IL-5 production induced by immobilized anti-CD3 monoclonal antibody was completely suppressed by the addition of anti-IL-2 monoclonal antibody, suggesting that IL-5 production, designated as a Th2-type immune response, is dependent on IL-2, a Thl cytokine. IL-2 produced at the site of allergic inflammation may contribute to IL-5 production by T cells in vivo.

Allergens↗

Enhanced production and gene expression of interleukin-5 in patients with bronchial asthma: possible management of atopic diseases by down-regulation of interleukin-5 gene transcription.

Interleukin (IL)-5 was produced in vitro by peripheral blood mononuclear cells (PBMCs) of mite-sensitive atopic patients upon challenge with specific allergen, while PBMCs of healthy controls produced essentially no IL-5. Stimuli delivered by the combination of phorbol ester (PMA) and CA2+ ionophore (ionomycin) induced marked IL-5 production by PBMCs obtained from atopic as well as nonatopic asthmatics. CD2- or CD4-bearing-cell depletion almost completely removed IL-5 production and gene transcription while CD8 depletion did not. These findings indicated that CD4+ T cells are the principal source of IL-5 in asthmatic PBMCs. The capacity of PBMCs of atopic asthmatics, nonatopic asthmatics and healthy controls to produce IL-2, IL-3, IL-4, interferon-gamma and granulocyte/macrophage-colony-stimulating factor was comparable among the three groups. FK506 suppressed IL-5 production and gene expression in vitro in a dose-dependent manner.

Allergens↗

Oral immunotherapy may induce T cell anergy.

Recently, the induction of T cell anergy has been considered as a sophisticated form of immunotherapy. However, the multiplicity of T cell allergen epitopes discourages the practical use of this method. Since orally administered antigen proteins are digested to peptides and absorbed into the circulation, oral administration of antigen might be an apparently primitive but practically very useful therapeutic approach. Freeze-dried body extract of Dermatophagoides farinae mite in tight capsules was orally administered at 0.5-3 mg/day to 17 adult male mite-sensitive asthmatic patients for 12 weeks. Marked and moderate improvement of clinical symptoms judged by symptom scores and peak expiratory flow was observed in 47% (8/17) of the patients. Bronchial provocation tests carried out before and after oral immunotherapy showed a statistically significant improvement especially in the late asthmatic response. The peripheral blood eosinophil count decreased significantly after oral immunotherapy. Interleukin-5 spontaneously produced by patient peripheral mononuclear cells decreased significantly (p < 0.05) after the oral immunotherapy. These results suggest that T cell anergy might be achieved by oral immunotherapy.

Administration, Oral↗