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Biomedical subjects

S Ahlstedt

Publications and source records attributed to S Ahlstedt.

At least 73 records · Page 4Linked to original sources
PubMed1990

Eosinophilic inflammation in asthma.

BACKGROUND AND METHODS: The importance of eosinophils in the pathogenesis of bronchial asthma is not established. In an attempt to evaluate the role of eosinophilic inflammation in asthma, we compared 10 normal subjects with 43 patients with chronic asthma, 19 of whom had severe disease as assessed by a clinical scoring method described by Aas and by pulmonary-function tests. Eosinophils were counted in peripheral blood and bronchoalveolar-lavage fluid, and in biopsy specimens obtained from the patients and post mortem from 8 subjects without asthma, but not from the 10 normal controls. Eosinophil cationic protein was titrated by radioimmunoassay in the bronchoalveolar-lavage fluid from all subjects and studied by immunohistochemistry in the biopsy specimens. RESULTS: There was a significant increase in the number of peripheral-blood eosinophils in the patients that was correlated with the clinical severity of asthma (P less than 0.001) and pulmonary function (P less than 0.03). Levels of eosinophils and eosinophil cationic protein were increased in the bronchoalveolar-lavage fluid from the patients and were also correlated with the severity of asthma (P less than 0.001 and P less than 0.002, respectively). Hematoxylin-eosin staining of bronchial-biopsy specimens showed that intraepithelial eosinophils were present only in patients with asthma. Immunohistochemical analysis of eosinophil cationic protein revealed that normal subjects had only a few nondegranulated eosinophils deep in the submucosa, whereas all the patients had degranulated eosinophils beneath the basement membrane and among epithelial cells. In some patients there was a relation between the presence of degranulated eosinophils and epithelial damage. CONCLUSIONS: Eosinophilic inflammation of the airways is correlated with the severity of asthma. These cells are likely to play a part in the epithelial damage seen in this disease.

Adult↗
PubMed1990

A fluorescence method for the visualization of inflammatory cells in intestinal mucosa.

Treatment of paraffin or cryostat sections from rat, rabbit and man, with fluorescein isothiocyanate (FITC) in buffer (1 microgram/l), resulted in visualization of highly fluorescent leukocytes with a granular staining in light microscopy. FITC staining of paraffin-embedded colonic tissue was compared with three other staining methods, i.e., (1) FITC-conjugated anti-neutrophil antibodies, (2) endogenous peroxidase with 3,3-diaminobenzidine, and (3) FITC-conjugated Lotus tetragonolobus lectin. Good correlations between FITC staining and the three other methods were found (r:0.97, 0.98 and 0.98; P less than 0.001). Inhibition of receptors for the FITC conjugates prior staining, by preincubation with unconjugated anti-neutrophil antibodies or L-fucose, abolished the staining with antibodies and lectin. This study shows that staining with unlabeled FITC represents a quick and convenient method for the estimation of phagocytic cells (polymorphonuclear cells and macrophages) in histological specimens.

Animals↗
PubMed1990

Peptidergic innervation of rat lymphoid tissue and lung: relation to mast cells and sensitivity to capsaicin and immunization.

The peptidergic innervation of lymphoid tissue and the lung in relation to mast cells was studied in rat. The sensitivity of neuropeptide-containing nerves to capsaicin treatment and immunization was also examined. Measurements of the content of neurokinin A and calcitonin gene-related peptide revealed that the lung contained the highest content of both neuropeptides; lymph nodes had intermediate levels, whereas the spleen had the lowest content. Immunohistochemistry showed that the calcitonin gene-related peptide- and neurokinin A-immunoreactive nerves in lymph nodes were mainly found around blood vessels, whereas in the lung the nerves were present within the lining respiratory epithelium, bronchial smooth muscle, around blood vessels and close to lymphoid aggregates. Combined immunohistochemistry for serotonin (5-hydroxytryptamine), as a marker for mast cells, and tachykinins or calcitonin gene-related peptide revealed that a close association was often present between the nerves and 5-hydroxytryptamine-positive cells in the bronchi of the lung, while 5-hydroxytryptamine-positive cells were not observed in lymph nodes. The neurokinin A and calcitonin gene-related peptide content in lymph nodes, spleen and lung, but not the content of neuropeptide Y, was markedly decreased by capsaicin treatment, suggesting a sensory origin for the two former peptides. Aerosol immunization increased the levels of calcitonin gene-related peptide in the lung, whereas the content in mediastinal lymph nodes was not affected. These data demonstrate a peptidergic innervation mainly of blood vessels in lymphoid tissue and a close relation between sensory nerves and mast cells as well as lymphoid aggregates in the bronchi of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Immune complex induced experimental colitis: beneficial effect of sulphasalazine in rabbits.

Experimental colitis was induced in rabbits by exposing the colon mucosa to 1% formalin followed by i.v. injections of soluble immune complexes made with antigen in excess. The animals were preimmunized with Escherichia coli O14:K7:H--inducing antibodies cross-reactive to intestinal epithelium. Animals with this colitis were divided in two groups. One group was treated with sulphasalazine and the other was given vehicle only. Sulphasalazine was administered daily at 125.5 mumol (50 mg) per kg body weight. The administration was started at the same day as the colitis was initiated. At Day 6, 13 and 30 following induction of colitis, biopsies were sampled and histologically evaluated. Inflammation was assessed by scores for inflammatory cells, crypt distortion, decreased crypt number and presence of crypt abscesses, thus corresponding to the picture seen in humans. A statistically significant lower score of inflammation was seen on Day 6 and 13 (P less than 0.01) and on Day 30 (P less than 0.05) following induction of colitis in animals treated with sulphasalazine.

Animals↗
PubMed1990

Accumulation of CD8+ cells after immunization with soluble antigen.

Rats were immunized with ovalbumin, either subcutaneously or by aerosol inhalation. The lymphocyte distribution in lymph nodes, peripheral blood, and spleen was investigated by flow cytometry after labelling with T pan (OX19 and W3/13), T helper lymphocytes (W3/25), T cytotoxic/suppressor lymphocytes (OX8), kappa light chain (MAR 18-5), or MHC class II (OX6) monoclonal antibodies. The influence of the neurotoxic agent capsaicin on the lymphocyte distribution was also analysed. Subcutaneous immunization resulted in an increased number of OX8+ cells in mesenteric lymph nodes, spleen, and peripheral blood but not in the draining lymph nodes, axillary, brachial, and mediastinal lymph nodes. The number of positive cells for the other cell markers used were not affected by immunization. The neuromodulatory effect of capsaicin had no effect on the lymphocyte distribution. The results showed that the type of immunization used, low amounts of antigen without adjuvant given during a prolonged period, selectively induced OX8+ cells. The patterns were unaffected by neuromodulation using capsaicin.

Animals↗
PubMed1990

Characteristics of immune-complex-induced chronic experimental colitis in rats with a therapeutic effect of sulphasalazine.

Experimental colitis was induced in rats by topical irritation of the colonic mucosa with 1 ml of 1% formalin followed by intravenous injection of 0.5 ml soluble immune complexes (IC) made in vitro in antigen excess and having characterized precipitation and complement activation profiles. The rats had been preimmunized with Escherichia coli O14:K7:H- to produce antibodies cross-reactive with colonic mucosa, thus aggravating the colitis to chronicity. Histologic evaluation of inflammation in the colon was performed on days 6, 12, and 18 by determining the number of phagocytic cells. The colitis was inhibited by sulphasalazine therapy given daily, 125.5 mumols (50 mg)/kg body weight, starting on the day when the inflammation was produced with IC and formalin. Sulphasalazine therapy significantly (p less than 0.05) decreased the number of phagocytic cells in the mucosa on days 12 and 18 but not on day 6. The results may give a clue to the beneficial pharmacologic effects of sulphasalazine in the treatment of ulcerative colitis.

Animals↗
PubMed1989

Isotype-specific suppression of IgE synthesis in a human myeloma cell line (U-266) by an IgE-binding protein derived from normal human peripheral blood cells.

Human peripheral blood cells produce immunoglobulin-binding factors upon stimulation with purified protein derivative. The binding factors from 2 healthy individuals were purified by IgE affinity chromatography. IgE-suppressive activity was demonstrable using the IgE-producing human myeloma cell line U-266 as an assay system. The effect of the suppressive factor seems to be reversible, isotype specific, as the immunoglobulin synthesis in the IgGk-producing U-1958 myeloma line was not affected, and selective for the epsilon heavy chain. The results also suggest that this suppression is not the result of a decrease in DNA synthesis or suppression of protein synthesis in general.

Humans↗
PubMed1989

Conditioned media from cultured blood cells of atopic individuals can induce differentiation in the human basophilic leukemia cell line KU812.

The basophilic propagating activity was determined in conditioned media obtained from cell cultures of mononuclear cells from atopic and healthy individuals. The activity was analyzed as the capacity to induce differentiation in the human basophilic cell line KU812. The KU812 cells responded primarily to cultured media with histamine production and secondarily with granulation. Eight atopic individuals, 3 of whom having mild symptoms, with known birch allergies were selected together with 3 control individuals. Total and specific IgE were analyzed in sera, and basophil and eosinophil counts were determined from blood smears after Wright's staining. Significant differences between the symptomatic atopic individuals and the control group were obtained for eosinophil counts (p less than 0.05) and in the KU812 basophilic differentiation activity assay (p less than 0.01). No single test could significantly discriminate between symptomatic and nonsymptomatic individuals, but the KU812 cell assay in combination with the eosinophil count clearly distinguished the symptomatic individuals from the control group. Increased levels of IgE specific to birch allergen were only obtained in the atopic individuals (p less than 0.001). No difference in basophilic propagating activity was observed with supernatants from cells incubated with birch pollen allergen. Serum tested for basophilic propagating activity showed no or decreased values of inducing histamine production in the KU812 cell line. In conclusion, the KU812 assay for basophilic propagating activity was the most useful discriminating test to select symptomatic atopic individuals from nonsymptomatic atopic and control individuals.

Basophils↗
PubMed1989

Effect of neonatal or later capsaicin treatment on bronchial reactivity in sensitized rats. Relation to humoral changes.

Treatment of ovalbumin-sensitized rats with capsaicin resulted in altered bronchial reactivity to both ovalbumin and serotonin. The increase in bronchial reactivity to ovalbumin in neonatally capsaicin-treated rats compared to animals only sensitized may be influenced by the changed ratios of IgA, IgE, and IgG antibodies, together with the inflammation in the lung. Thus, capsaicin given neonatally inhibited the formation of antibodies, both specific titers and total levels, in bronchial lavage.

Age Factors↗
PubMed1989

Increased delayed-type hypersensitivity reaction in rats neuromanipulated with capsaicin.

We studied the neuroimmunomodulatory effect of capsaicin on the development of delayed-type hypersensitivity (DTH) reaction and antibody formation after reduction of neuropeptides in the peripheral sensoric nervous system. Rats were sensitized with picryl chloride on their shaved abdomen or by subcutaneous injections with picrylsulfonic acid (PSA). Manipulation of the content of neuropeptides in the sensory nerve system with capsaicin was performed 1 week before or after sensitization. An increase of the DTH reaction assessed as increased ear thickness after challenge was seen especially when the rats were given capsaicin after sensitization. The formation of specific antibodies was not affected, although the level of total IgG was decreased in PSA-sensitized rats treated with capsaicin after sensitization. The results demonstrated that the DTH reaction in rat was slightly but significantly affected by the abolishment of neuropeptides in sensoric nerve endings with capsaicin. Even if the direct effect of capsaicin on the immune system still has to be elucidated, these results indicate that neuropeptides in sensory nerves are involved in the pathogenesis of DTH.

Animals↗
PubMed1988

Isolated late cutaneous skin test response to ampicillin: a distinct entity.

A case presentation describes a young woman with a history of two reactions to ampicillin therapy and a reproducible skin test reaction of intermediate timing that disappeared within 48 hours. The skin test response was to ampicillin only and not to other penicillin-related skin test reagents. Tests for serum IgE and IgG antibody to ampicillin were negative. The histology was that of a mononuclear and neutrophilic cellular infiltrate with neutrophil margination in the vessels. There was no immunoglobulin, complement, or fibrin deposition. The skin test reaction began and ended earlier than would be expected for a classic delayed hypersensitivity reaction. It is considered to be an isolated late cutaneous response but cannot yet be designated a late cutaneous allergic response. Reactants characteristic of an Arthus reaction were not present, and no alternative immunologic basis was confirmed.

Adult↗
PubMed1988

Altered lymphocyte proliferation of immunized rats after neurological manipulation with capsaicin.

The neurotoxic agent capsaicin was used for depletion of the content of neuropeptides in c-fibers of the sensory nerve system in rats. The effect of the capsaicin treatment on the immune response was assessed as lymphocyte proliferation of spleen cells, stimulated with Con A. Treatment of 2 day old rat pups and adult rats did not alter the lymphocyte proliferative response to Con A in nonimmunized rats. Spleen cells from capsaicin-treated and subcutaneously immunized rats showed a decreased proliferation response to Con A. Capsaicin treatment of aerosol immunized rats did not affect the proliferation level of the spleen cells to the same extent. The results indicate that abolishment of the content of neuropeptides in the c-fibers of sensory nerves with capsaicin, affects the immune response.

Animals↗
PubMed1988

Induction of basophilic differentiation in the human basophilic cell line KU812.

The potential for differentiation of the human basophilic leukaemia cell line KU812 was examined by means of a panel of physiologic and non-physiologic substances used as inducers. The phenotypic characteristics of non-induced KU812 cells included an immature morphology with scanty cytoplasmic granulation, expression of a low amount of high affinity, but no low affinity receptors (CD 23) for IgE, and a capacity for low-rate histamine synthesis. The differentiation process was characterized by a rapid (24 h) increase in histamine production a slower morphological maturation with the development of Alcian blue stainable granula demonstrable after 72 h. Concomitant with the phenotypic alterations, cell growth was inhibited. Differentiation in KU812 cells was inducible by Ara-C and to some extent by sodium butyrate, but not by dimethyl sulphoxide, retinoic acid, or gamma-interferon. Conditioned medium (CM) from cultured peripheral blood cells from atopic individuals and 18 out of 22 analysed glioma cell lines induced differentiation of the KU812 cells, whereas supernatant from only 1 out of 21 other cell lines, including carcinoma, melanoma, sarcoma, leukaemia, and normal fibroblasts had this activity. CM from the T-leukaemic cell line, Mo, also induced KU812 differentiation. A primary fractionation of the active substance from this cell line by reversed phase chromatography eluted the active substance at a concentration of 42-44% acetonitrile. Our present study has shown that the KU812 may serve as an appropriate model to study differentiation of basophils. In addition, its fast and specific response to biological factors makes it suitable as a biological assay for determination of active factor produced by atopic individuals.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

Immunological suppression of delayed hypersensitivity responses in mouse lungs as reflected by numbers of mononuclear cells, mast cells and mucus-producing cells.

The suppression of delayed hypersensitivity (DH) in the lung as reflected by the appearance of mononuclear cells, mast cells and mucus-producing cells was studied in Balb/c mice. Immunosuppression was induced by intravenous and peroral administration of picrylsulfonic acid (PSA) in mice subsequently sensitized with picrylchloride (PiCl). The animals exhibited a decreased DH reactivity as assessed by ear thickness increase compared with mice sensitized but not exposed to PSA pretreatment. In mice exposed to PSA intravenously (suppressed) and sensitized with PiCl there was a decrease in the number of mononuclear cells in the lung after challenge, compared to mice sensitized and challenged only. Similarly, the mast cell and mucus-producing cell numbers were slightly lower in animals immunosuppressed intravenously with PSA compared with sensitized mice. Such a decrease in the numbers of mononuclear cells, mast cells and mucus-producing cells in the lung was not seen in animals treated with PSA perorally, although these animals exhibited suppressed DH reaction in the ears. The present results indicate that induction of mononuclear cells and to some extent mast cells and mucus-producing cells in the lung relates to the DH reaction and its regulation.

Animals↗
PubMed1988

Regulation by T cells of delayed hypersensitivity reaction in mouse lung as reflected by mononuclear cells, mast cells and mucus-producing cells.

The appearance of mononuclear cells, mast cells and mucus-producing cells in the lung and their linkage to the development of delayed hypersensitivity (DH) reactions were studied. Adoptive transfer of immune lymph node cells, spleen cells and serum and in vivo treatment with monoclonal antibodies to L3T4-positive T cells in Balb/c mice were performed to investigate the cellular regulation of the number of mononuclear cells, mast cells and mucus-producing cells in the lung. Immune lymph node cells and, to a lesser extent, immune spleen cells from mice sensitized epicutaneously with picrylchloride transferred DH reactions to the recipients as assessed by ear thickness increase after challenge. Serum from sensitized mice was not able to transfer a DH reaction. Cyclophosphamide treatment of donor mice increased the DH reaction in the recipient mice. Adoptive transfer of immune lymph node cells and spleen cells gave a slight increase in the number of mononuclear cells in the lung of recipient mice compared with controls. This weak accumulation of mononuclear cells in the lungs of recipient mice, however, was not accompanied by a consistent increase in the number of mucus-producing cells and mast cells. The number of spleen cells expressing the L3T4 antigen decreased after in vivo treatment with the monoclonal GK1.5 (anti-L3T4) antibody as assessed by immunohistochemistry. This antibody treatment also resulted in an inhibition of the DH reaction and a decrease in the number of mononuclear cells and mucus-producing cells, but not in mast cells in the lung of sensitized and challenged mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗