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Biomedical subjects

S Ahlstedt

Publications and source records attributed to S Ahlstedt.

At least 109 records · Page 6Linked to original sources
PubMed1986

Cyclophosphamide-mediated enhancement of delayed hypersensitivity reactions in the lung.

The appearance of mononuclear cells, mast cells and mucous cells in the airways was studied in Balb/c mice in relation to cell-mediated immunity reflected as delayed hypersensitivity (DH). The animals were pretreated with cyclophosphamide (Cy) to increase cell-mediated immunity and to decrease the influence of antibodies. Mice pretreated with Cy and epicutaneously sensitized with picrylchloride (PiCl) had stronger DH reactions as compared with sensitized mice not pretreated with Cy. The Cy treatment decreased the IgG antibody formation after sensitization. The Cy-pretreated, sensitized and challenged mice had increased numbers of mucus-producing cells and to some extent also mononuclear cells in their lungs compared with sensitized and challenged non-Cy-treated animals. However, the mucous cell numbers were also increased in Cy-treated, but nonsensitized mice in which most of the airway epithelium had differentiated into mucus-containing cells. The present results indicate that local cell-mediated immunity involves the appearance of mononuclear cells and mucus-producing cells in the lung. This inflammatory reaction is enhanced by Cy treatment, although mucous cell differentiation seems to be induced by exposure to Cy alone.

Animals↗
PubMed1986

Appearance of mast cells in bone marrow, peripheral blood and spleen of immunized rats.

The appearance of mast cells and their progenitors was studied in rats. The animals were immunized according to a protocol utilizing 2-week periods of daily administration of small doses of ovalbumin either as aerosol or as subcutaneous injection without adjuvant. These procedures are known to induce allergic responses of the IgE-mediated type. The immunization procedures resulted in increased numbers of mature mast cells in bone marrow. There were also increased numbers of progenitors, as indicated by increased maturation of mast cells in cultures of bone marrow cells from immunized animals compared with nonimmunized controls. Bone marrow cells in cultures from immunized and nonimmunized animals showed similarly increased maturation of mast cell progenitors when stimulated with conditioned medium from mixed lymphocyte reaction cultures. The number of progenitors was considerably lower in peripheral blood and spleen than in bone marrow. However, cultures of cells from peripheral blood and spleen of aerosol-immunized rats contained cells which matured into mast cells after addition of medium from mixed lymphocyte reaction cultures. The study shows that in immune responses similar to those seen in allergic individuals mast cells are normal constituents.

Aerosols↗
PubMed1986

Enhancement of the bronchial reactivity in immunized rats by neonatal treatment with capsaicin.

Rats were injected with capsaicin at 1-2 days of age to abolish the content of substance P (SP) in nerve terminals. At 6 weeks of age the capsaicin-treated and control rats were sensitized daily for 1 or 2 subsequent weeks Monday through Friday with ovalbumin (OA). The OA was given without adjuvant as 300 ng subcutaneous (s.c.) injections in the neck region or as 1% aerosol for 30 min. The capsaicin-treated animals which were sensitized s.c. for 2 weeks reacted moderately with increased transpulmonary pressure (TPP) to airway challenge with OA, and strongly to intravenous (i.v.) challenge with OA or serotonin. The capsaicin-untreated animals, which were sensitized with OA, reacted weakly to the challenge. In the challenge. In the animals sensitized with aerosolized OA, slightly lower reactivity was seen compared with those sensitized s.c. Untreated and unsensitized control rats reacted only to serotonin challenge. No animal had any detectable serum or bronchial IgE antibodies. Aerosol-sensitized animals had IgG antibodies in both serum and bronchial lavage. Histologically, the animals treated with capsaicin in contrast to the untreated controls demonstrated a pronounced increase of lymphoid tissue around their bronchi. Their mast cell numbers were increased around vessels and in the pleura and their mucous cell numbers were increased in the epithelium of the bronchi and bronchioli. The sensitization did not add much to this histological picture.

Animals↗
PubMed1986

Stimulation of maturation of large immature histamine-containing basophilic cells from human peripheral blood, cord blood and bone marrow.

The development of FcR epsilon-bearing histamine-containing basophilic cells was studied in cultures of peripheral blood leucocytes and bone marrow leucocytes from normal individuals. The determination of basophilic cells was performed blindly. Before cultivation there were fairly similar numbers of basophilic cells in the samples from the three different sources (1.6 +/- 1.6 n = 13; 1.4 +/- 2.0 n = 21; 4.3 +/- 4.7 n = 8, respectively). During cultivation spontaneously appearing large blast-like basophilic cells were seen in good correspondence with a formation of histamine in the cultures (Spearman rank correlation coefficient = 0.9135, n = 13, P less than 0.001). This was more accentuated with bone marrow cells than with peripheral blood and cord blood cells. Conditioned medium (CM) was prepared from cells isolated from various tissues and stimulated by different means, e.g. peripheral blood from atopic individuals stimulated with allergen and unstimulated tonsil cells. Addition of the CM resulted in increased development of histamine-containing basophilic cells. Optimum stimulation was achieved with 10% CM. The basophilic stimulation by CM, as assessed as indices vs. unstimulated cultures, was more accentuated in cultures of peripheral blood cells than of bone marrow and cord blood cells (2.8 +/- 1.2; 1.8 +/- 0.5; 2.0 +/- 0.4, respectively). In contrast, the histamine formation was particularly evident in stimulated cultures of bone marrow cells, where more than four-fold increases of histamine were found. In bone marrow cells the histamine levels per basophilic cell also increased, whereas this was not the case in cord blood cells. A pronounced development of basophilic cells was achieved when using leukoagglutinin, provided the mitogen in the CM was eliminated. The formation of basophilic cells was prevented with mitomycin c and cycloheximide. In conclusion, the system described may provide important information on the development of histamine-containing basophilic cells at various maturation stages from different compartments, and mechanisms in a developing atopic disease.

Basophils↗
PubMed1986

Basophil/mast cell precursors in mast cell proliferative disorders.

Mast cell proliferative disorders include urticaria pigmentosa, localized to the skin, and systemic mastocytosis, with progression from urticaria pigmentosa to systemic mastocytosis in some adults. We have evaluated the presence of basophil/mast cell precursors in urticaria pigmentosa and systemic mastocytosis using an in vitro assay for cells which form histamine-positive peripheral blood granulocyte colonies in methylcellulose. In 17 cultures from 10 patients with mast cell proliferative disorders (6 urticaria pigmentosa, 4 systemic mastocytosis), the frequency of histamine-positive granulocyte colonies was significantly higher in systemic mastocytosis (40% colonies picked) than in urticaria pigmentosa (15%, p less than 0.002). The mean histamine content per cell of urticaria pigmentosa patient colonies was less than or equal to 0.1 pg compared to 0.7 +/- 0.1 pg in systemic mastocytosis patient colonies. Precursor assays done serially at different times in individual patients appeared to reflect clinical extent of disease. In one patient with urticaria pigmentosa, a repeatedly normal number of histamine-positive colonies paralleled no change in clinical course, while in 2 others (1 systemic mastocytosis, 1 urticaria pigmentosa) increasing skin lesions, leukopenia, increased urinary histamine or refractoriness to therapy was accompanied by an increase in the frequency of basophil/mast cell precursors. Using an index of disease activity, the frequency of histamine-positive colonies was significantly higher in active, versus inactive, mast cell proliferative disorders (p less than 0.0001). These studies confirm the biologic relevance of mast cell proliferation in mast cell proliferative disorders, and suggest that precursor assays using histamine content of granulocyte colonies may be useful in predicting extent of disease.

Adolescent↗
PubMed1985

Regional and systemic immune responses to trinitrophenyl derivatives after intranasal and subcutaneous sensitization of mice.

The immune responses and accompanying inflammatory local reactions were analyzed in mice sensitized subcutaneously (SC) or intranasally. Administration of picrylsulfonic acid (PSA) by both routes for two 2- or 1-week periods with a 4-week interval resulted in delayed hypersensitivity responses. Serum antibodies of the IgG and IgE and some of the IgA isotype were found, particularly in SC-sensitized animals. The latter animals also had levels of IgG antibodies in their bronchial fluid. Lymph node cells from mice sensitized for 2-week periods demonstrated high spontaneous proliferation. After culture together with spleen cells, these cells exhibited considerable numbers of mast cells, particularly after stimulation with pokeweed and antigen. The lungs from mice sensitized intranasally revealed increased numbers of mononuclear cells around large vessels and mucous cells in the bronchiolar epithelium, although there were individual differences between the animals. The mast cell numbers in the lungs were only slightly increased compared with numbers in nonimmunized animals subjected to ether anesthesia. Animals injected SC with PSA exhibited increased numbers of mast cells in their lungs compared with control mice. Mice sensitized with trinitrophenylated human serum albumin demonstrated some differences in their immune reactivity compared with animals immunized with PSA. Thus, no obvious delayed hypersensitivity appeared, but the IgG antibody titers were higher, and the IgE antibody titers were lower. The cellular responses assessed histologically demonstrated higher mononuclear cell numbers and lower mast cell numbers compared with those observed in animals sensitized with PSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1985

Increased IgE antibody responses in rats exposed to tobacco smoke.

Raised serum IgE levels were found in a high proportion of rats that had been exposed to tobacco smoke twice daily 5 days a week for 8 wk in a Dontenville-type smoking machine. Levels above 1 ng/ml of IgE were found in nine of 20 animals exposed to cigarette smoke and in five of 20 rats exposed to smoke from cigarettes with 1.45% phenylmethyloxidiazole added for possible protection against the effects of the smoke. None of the 20 control rats exhibited similarly increased serum IgE. Exposure to tobacco smoke did not significantly affect the serum concentrations of IgM and IgG. The development of specific IgE and IgG antibodies was also influenced by tobacco smoke exposure. Rats exposed to ovalbumin aerosol developed increased levels of IgG and IgE antibodies, whereas no effect on the development of antibody titers was found in rats immunized by the subcutaneous route. This study demonstrates that exposure to tobacco smoke increases serum IgE levels and enhances sensitization via the airways by a local effect, thus supporting the "mucosal theory of atopy."

Animals↗
PubMed1985

Immune stimulated regional inflammatory responses mediating lung reactivity in rats.

Daily sensitization of SPF BNxWi/Fu rats with ovalbumin (OA) in aerosol during 2-week periods with a 4-week interval resulted after 7 weeks in IgE, IgA and IgG antibodies in serum and bronchial fluid. After cultivation of the regional, axillary, brachial and mediastinal (ABM) lymph node cells, IgE antibodies were found in the culture supernatant. Such antibodies were not found in culture supernatants of spleen and inguinal lymph nodes. Regional formation of IgE antibodies was also noted in the ABM lymph node cell culture supernatants after subcutaneous (s.c.) injections of 100 ng OA in the neck region. When the injections were given in the tail-root region, the inguinal but not the ABM lymph nodes produced the IgE antibodies. The s.c. sensitization induced inconsistent and rather low IgG and no IgA antibody responses. The aerosol but not the s.c. sensitization induced accumulations of mononuclear cells and mucous cells in the lungs. Clinically, the rats sensitized s.c. in the neck region reacted to aerosol and intravenous (i.v.) challenge as early as 1 week after sensitization had started, whereas the animals sensitized in the tail-root regions reacted 7 and 8 weeks after repeated sensitization. The animals sensitized by aerosol showed only weak clinical reactivity after i.v. challenge.

Animals↗
PubMed1985

Relation between components of the immune response in rats sensitized by aerosol and subcutaneous injections.

Relations between the appearance of various components of the immune response were analyzed in two groups of rats sensitized by aerosol and subcutaneous injections in the neck region, respectively. The relations were expressed by Spearman rank correlation coefficient and studied by cluster analysis. In the aerosol-sensitized animals, there was a close association between IgA and IgG antibody levels in bronchial fluid and these in turn were related to IgG levels in serum and more loosely to IgE levels in bronchial fluid. There was an apparent association between IgE antibody formation and mast cell maturation in cultures of regional lymph node cells and the appearance of mucous cells in the lungs. These variables seemed associated with spontaneous cell proliferation in vitro and the numbers of mast cells in the lungs. This indicates that local stimulation with antigen induces local immune responses and immune-mediated migration of cells. In subcutaneously sensitized animals, formation of IgG antibodies in vitro seemed related to the stimulated proliferation of regional lymph node cells. The levels of IgG and IgE antibodies in bronchial fluid and in serum also appeared to be related. Unlike the findings in aerosol-sensitized animals there was no apparent relation between the differentiation of mast cells and mucous cells. This was possibly due to lack of immune-mediated antigen-induced cell migration. The different immune response patterns in aerosol and subcutaneously sensitized rats should be considered when studies are designed aiming to explore the pathogenesis of allergic inflammatory diseases. The findings also indicate that the various parameters of immunity are more closely related in aerosol than in subcutaneously immunized animals.

Aerosols↗
PubMed1985

Appearance of basophilic cells/mast cells and IgE antibodies in liquid human cell cultures.

Maturation of basophils/mast cells as well as formation of IgE antibodies are parts of the immune response to antigens. We have analyzed these important constituents of the allergic inflammatory response in vitro, cultivating human peripheral blood cells from allergic and normal individuals. Mesenteric lymph nodes were also cultured from two normals. In liquid cultures of peripheral blood cells, the number of small basophils initially present decreased and large basophilic cells appeared over a 2-week period. In normals, the maturation of large basophils from precursor cells could be stimulated with supernatants from peripheral blood cell cultures from atopic individuals stimulated with the relevant allergen. The IgE levels declined in cultures of peripheral blood, whereas the IgE antibodies in cultures of cells from a mesenteric lymph node from one of the nonallergic individuals increased during the 2-week period. In separate cultures, the IgE formation could not be reproducibly stimulated by antigen or mitogen. The study shows the possibility to stimulate the maturation of basophil/mast cell precursor cells present in the blood of allergic and healthy individuals with antigen-induced factors. In contrast, the IgE formation by blood cells was difficult to stimulate.

Basophils↗
PubMed1985

Proliferative synovitis in rabbit knee joints induced by antigen and preformed immune complexes.

Knee joints of non-immunized rabbits were repeatedly injected with bovine serum albumin (BSA) and preformed BSA-anti-BSA immune complexes which had differing precipitation profiles and abilities to activate complement. Ten days after the last of six injections the antibody and lymphoproliferative responses to BSA were analysed and correlated to the degree of arthritis. Joint swelling, increased numbers of joint fluid leukocytes and morphological changes typical of proliferative synovitis were found only in those rabbits injected with a large dose of antigen or with immune complexes prepared in antigen excess of poor precipitation and complement-activating properties in vitro. The degree of arthritis correlated with the development of humoral and lymphoproliferative immune responses to BSA.

Animals↗
PubMed1985

Protective factors in milk and the development of the immune system.

The neonate is immature in certain immunologic functions. The slow development of secretory immunoglobin A (IgA) seems to be compensated by selective transfer of secretory IgM into exocrine secretions on mucous membranes during the first few months of life. Secretory IgA and secretory IgM antibodies against Escherichia coli and poliovirus are already found in the neonate, possibly in response to the maternal anti-idiotypic IgG antibodies transplacentally exposing the fetus. Via such a mechanism, food antibodies could occur before direct food exposure in the infant. Human milk provides large amounts of antibodies (as a crude comparison, about 50 times the amount of antibodies given to a patient with hypogammaglobulinemia). The milk antibodies, dominated by secretory IgA, protect especially against intestinal infections. The milk also contains oligosaccharide analogues to epithelial receptors for bacteria. They, as well as a number of milk components such as lactoferrin and lysozyme, may contribute to host defense. The food antibodies in human milk may influence the infant's immune response to foreign food proteins introduced during weaning.

Animals↗
PubMed1984

Inhibitory effect of honey bee venom on immune complex mediated leukocyte migration into rabbit knee-joints.

The anti-inflammatory effect of purified honey bee venom (HBV) was studied using a recently described animal model in which preformed immune complexes were injected into rabbit knee-joints. As little as a single injection of 1.2 micrograms HBV/kg body weight subcutaneously significantly reduced the immune complex induced joint inflammation as measured by reduction in leukocyte counts in the joint fluid. This decrease was obvious 3 and 6 but not 9 hours after induction of the inflammation. There was no significant effect on leukocyte random migration, chemotactic responsiveness or phagocytosis, indicating that HBV did not interfere with normal phagocyte motility and ingestion. The modifying effects by HBV on the inflammatory response to immune complexes in vivo is most likely due to interference with other components of the inflammatory response.

Animals↗
PubMed1984

Bronchial reactivity in relation to immune responses in rats after subcutaneous sensitization without adjuvant.

Rats of BNxWi /Fu strain were immunized by daily subcutaneous (s.c.) injections of antigen without the use of adjuvant for two 2-week periods with a 4-week interval. The bronchial responses to airway and intravenous (i.v.) antigen challenge were measured during and after the immunization period. These responses were compared with both the humoral and the cell-mediated immune response of the animals. Immunization induced bronchial reactivity of the animals to antigen after airway and i.v. challenge. This reactivity persisted for 7 weeks following the second immunization period. Specific IgE antibodies were detected in serum, bronchial fluid and in supernatants from cultured peripheral lymph node cells. The immunization also resulted in an IgG antibody response. Neither the amount of IgE, IgG2a, nor of any other isotype, correlated with the bronchial reactivity in the animals. Antigen stimulation of lymph node cells mixed with syngeneic spleen cells induced proliferation. This procedure also resulted in a maturation of mast cells in 3-week cultures. The immunization also resulted in some increase in the number of mast cells around vessels in the lung. There was no correlation between these parameters of cell-mediated immunity and either antibody responses or bronchial reactivity.

Adjuvants, Immunologic↗
PubMed1984

Influence of breast feeding on the development of cow's milk protein antibodies and the IgE level.

In 48 infants unselected with regard to atopic heredity, the levels of serum IgG, IgA and IgM antibodies against native cow's milk proteins and IgG antibodies against beta-lactoglobulin were measured with ELISA and the total serum IgE concentration with Phadebas PRIST. Using multiple regression analysis the level of each type of antibody was related to the age at weaning, at first exposure to cow's milk and at sampling. The longer the infants were exposed to cow's milk protein without concomitant breast feeding and the younger they were at the introduction of cow's milk formula, the higher were the IgG antibody levels against native cow's milk proteins. The investigated variables explained only 17% of the variation of the antibody level, however. The IgG antibodies against beta-lactoglobulin showed significant negative correlations to the age at weaning and the age at first cow's milk exposure, explaining 8% of the variation. Specific IgA and IgM antibody levels an those of total serum IgE did not show any significant relation to the investigated independent variables.

Animals↗