Allergic response to common environmental agents has been regarded as a main pathogenetic mechanism of bronchial asthma. However, allergic sensitization (atopy) can not be detected in a siginificant number of adult asthmatic patients. The etiology of nonatopic asthma has not yet been defined. To evaluate the possible involvement of autoimmune response against bronchial mucosa in the pathogenesis of nonatopic asthma, we performed indirect immunofluorescence staining of fresh frozen human bronchial mucosa tissue using serum samples from patients with atopic and nonatopic asthma, healthy controls, and patients with systemic lupus erythematosus. On immunostaining, circulating IgG autoantibodies against bronchial mucosa were detected in 2 (9.1%) of 22 patients with nonatopic asthma and in none of 22 patients with atopic asthma and of 22 healthy controls. IgG autoantibodies from the two patients with nonatopic asthma predominantly stained the cytoplasmic membrane of basal cells in bronchial epithelium. Serum samples from 10 patients with systemic lupus erythematosus immunostained the nucleus of epithelial cells in whole layer of bronchial epithelium. This study showed the presence of circulating IgG autoantibodies against the bronchial epithelial cell in a small portion of patients with nonatopic asthma. Further studies may be necessary to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma.
Asthma/immunology* ; Autoantibodies/immunology* ; Autoantibodies/blood ; Bronchi/immunology* ; Epithelial Cells/immunology ; Human ; Immunity, Mucosal/immunology ; Respiratory Mucosa/immunology*

The pathogenetic mechanism of nonatopic asthma has not yet been defined. The idea of a possible involvement of autoimmunity in the pathogenesis of nonatopic asthma has been proposed by earlier studies. To evaluate the possible involvement of autoimmune response against bronchial epithelial cell in the pathogenesis of nonatopic asthma, we measured circulating autoantibodies to cultured human bronchial epithelial cell (BEAS-2B cell line) using enzyme-linked immunosorbent assay. We used stored serum samples form 38 age-matched healthy controls, 26 adult patients with atopic asthma, 16 adult patients with nonatopic asthma, and 12 adult patients with systemic lupus erythematosus. Levels of IgG autoantibodies to bronchial epithelial cell were significantly higher in patients with nonatopic asthma (mean+/-SD of absorbance values; 0.135+/-0.030) and systemic lupus erythematosus (0.293+/-0.181) than in healthy controls (0.112+/-0.016) and patients with atopic asthma (0.116+/-0.031) (p<0.05). This study showed that levels of circulating IgG autoantibodies to bronchial epithelial cell were increased in adult patients with nonatopic asthma. Further studies are needed to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma.
Adult ; Asthma/*immunology ; Autoantibodies/*blood ; Bronchi/*immunology ; Cells, Cultured ; Epithelial Cells/immunology ; Human ; Hypersensitivity/immunology ; IgG/blood

There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. We conducted methacholine challenge test and nasal eosinophils on nasal smear to patients with allergic rhinitis in order to investigate the mechanism of connecting upper and lower airway inflammation in 35 patients with AR during exacerbation. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness (BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients had normal pulmonary function. Significant differences in BHR were detected in the comparison of patients with cough or postnasal drip and without cough or postnasal drip. There were significant differences of PC20 between patients with cough or postnasal drip and those without cough or postnasal drip (3.41 +/-3.59 mg/mL vs 10.2 +/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in patients with seasonal AR than in patients with perennial AR with exacerbation (472.5 +/-132.5 IU/L vs. 389.0 +/-70.9 IU/L, p<0.05). Nasal eosinophils were closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that nasal eosinophilic inflammation might contribute to BHR in patients with AR.
Adult ; Bronchi/*immunology ; Bronchial Hyperreactivity/*immunology ; Eosinophils/*immunology ; Female ; Humans ; Immunoglobulin E/blood ; Inflammation ; Male ; Rhinitis, Allergic, Perennial/*immunology ; Rhinitis, Allergic, Seasonal/*immunology ; Spirometry ; Time Factors

OBJECTIVETo investigate bronchial responsiveness to acetylcholine in allergic airway inflammation of SD rats.

METHODSSD rats were immunized and challenged by chicken ovalbumin (OVA). Airway responsiveness, acetylcholine (Ach) provocation concentration needed to increase baseline airway resistance by 200% (PC(200)) were measured.

RESULTSThe value of baseline airway resistance in asthma group was significantly higher than that in control group (2.282 +/- 0.128 vs 3.193 +/- 0.239; P < 0.01). After multiple ovalbumin exposures, airway responsiveness to intravenous injection of acetylcholine decreased significantly (-LogPC(200): 4.006 +/- 0.554 vs 2.059 +/- 0.262; P < 0.01). Bronchial alveolar lavage fluid (BALF) and lung tissue specimen analysis indicated that airway allergic inflammation was present.

CONCLUSIONSThe study demonstrates a dissociation between the bronchoconstrictor response and bronchial hyper-responsiveness and indicates that multiple ovalbumin exposures induces persistent bronchoconstriction with airway hypo-responsiveness despite airway allergic inflammation.

Acetylcholine ; pharmacology ; Airway Resistance ; Allergens ; immunology ; Animals ; Bronchi ; drug effects ; physiology ; Bronchial Hyperreactivity ; etiology ; Bronchoconstriction ; Lung ; pathology ; Male ; Ovalbumin ; immunology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the activation of Toll like receptor 4 (TLR4) on passively sensitized human airway smooth muscle cells (HASMCs) proliferation and the synthesis and secretion function.

METHODSThrough the cultivation of primary HASMCs, we studied TLR4 expression on cell surface, cell proliferation and transformation of parturient factor-beta1 (TGF-beta1) in asthma under the condition of synthesis and secretion level by passively sensitized HASMCs with asthma serum.

RESULTSCompared with the control group, in passive sensitized group and TNF-alpha group TLR4 expression were significantly increased (P < 0.01), significantly enhanced proliferation (P < 0.01), total protein concentration, IgE secretion and TGF-beta1 were significantly higher (P < 0.01); and all the above parameters were increased more significantly in TNF group compared with those in the target effect of passively group; and those parameters were significantly reduced in anti-TLR4 antibody group compared with those in the target effect both of passively sensitized group and TNF-alpha group.

CONCLUSIONTLR4 on passively sensitized HASMCs activated can induce the excessive proliferation of HASMCs and a large number of synthesis and secretion of TGF-beta1, resulting in changing airway micro-environment, which involved in airway remodeling in asthma.

Airway Remodeling ; Asthma ; metabolism ; pathology ; Bronchi ; cytology ; Cell Proliferation ; Cells, Cultured ; Humans ; Myocytes, Smooth Muscle ; cytology ; metabolism ; Toll-Like Receptor 4 ; immunology ; Transforming Growth Factor beta1 ; metabolism

A number of case reports on occupational asthma caused by herbal medicines have been issued, for example, on Sanyak, Chunkung, Banha, and Brazilian ginseng. Recently, cases of occupational asthma induced by Sanyak and Korean ginseng have been reported, but the pathogenic mechanisms involved are unknown. This study was carried out to evaluate the immunologic mechanism underlying Korean ginseng-induced occupational asthma. A patient engaged in Korean ginseng wholesale was referred for recurrent dyspnea, wheezing, and nasal symptoms, which were aggravated at work. Allergen bronchial provocation testing to Korean ginseng extract showed a typical immediate response, and skin prick testing to Korean ginseng extract also showed a strong positive response. Moreover, serum-specific IgE levels to Korean ginseng extract were significantly higher than in controls. Enzymelinked immunosorbent assay (ELISA) inhibition tests showed a dose-dependent inhibition by Korean ginseng, but not by Dermatophagoides farinae, wheat flour, or Chinese balloon flower. Sodium dodecylsulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and immunoblotting revealed four specific Immunoglobulin E (IgE) binding components at 26, 30, 47, and 60 kDa, which were not bound by control sera. These results strongly suggest that occupation asthma induced by Korean ginseng is induced via an IgE-mediated mechanism.
Animals ; Asthma/diagnosis/*etiology/*immunology ; Bronchi/metabolism ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay/methods ; Flour ; Flowers ; Humans ; Hypersensitivity/*diagnosis ; Immunoglobulin E/analysis/*chemistry ; Korea ; Occupational Diseases/diagnosis/*etiology/*immunology ; Panax/*adverse effects ; Pyroglyphidae/metabolism ; *Skin Tests

This investigation was designed to confirm IL-8 production from human bronchial epithelial cells with toluene diisocyanate (TDI) exposure and to examine the effects of pro-inflammatory cytokine and dexamethasone. We cultured Beas-2B, a bronchial epithelial cell line with TDI-HSA conjugate and compared with those without conjugate. IL-8 in the supernatant was measured by ELISA. To evaluate the effect of proinflammatory cytokines, peripheral blood mononuclear cells (PBMC) were collected from TDI- and non-TDI asthma patients, and were added to the epithelial cell culture. Dexamethasone or antibodies to TNF-alpha and IL-1beta were pre-incubated with PBMC supernatant. There was a significant production of IL-8 from bronchial epithelial cells with addition of TDI-HSA conjugate in a dose-dependent manner, which was significantly augmented with addition of PBMC supernatant. Higher production of IL-8 was noted with addition of PBMC supernatant from TDI-asthma patients than in those from non-TDI asthma patients. IL-1beta and IL-1beta/TFNalpha antibodies were able to suppress the IL-8 productions. Pre-treatment of dexamethasone induced dose-dependent inhibition of the IL-8 production. These results suggest that the IL-8 production from bronchial epithelial cells contribute to neutrophil recruitment occurring in TDIinduced airway inflammation. IL-1beta released from PBMC of TDI-induced asthma patients may be one of the pro-inflammatory cytokines to enhance IL-8 production.
Asthma/immunology ; Bronchi/*cytology/metabolism ; Cell Line ; Dexamethasone/pharmacology ; Epithelial Cells/cytology/*drug effects/*metabolism ; Glucocorticoids/pharmacology ; Human ; Interleukin-8/*metabolism ; Leukocytes, Mononuclear/cytology/metabolism ; Support, Non-U.S. Gov't ; Toluene 2,4-Diisocyanate/*toxicity

OBJECTIVETo investigate the effect of prostaglandin D2 receptor antagonists on the airway inflammation in rats with asthma.

METHODSForty male SD rats were randomly divided into four groups: Group A (normal control), Group B (asthma group), Group C (CRTH2 antagonist BAYu3405 treatment group), Group D (DP1 antagonist BWA868C treatment group). Asthma was induced by ovalbumin (OVA) challenge. The rats in each group were sacrificed 24 h after the last challenge of OVA.DP1/CRTH2 receptors on eosinophils (EOS) were measured by radiological binding assay (RBA). The left lungs were used for histological examinations and bronchoalveolar lavage fluid (BALF) was collected from the right lungs. The total cell numbers, EOS absolute count and differential cell counts in BALF were performed. Serum concentrations of IL-4, 5 and IFN-gamma were measured by ELISA.

RESULTSRats in BAYu3405 treatment group showed profoundly decreased infiltrates of EOS and lymphocytes in the wall of bronchus when compared with those of asthma group and BWA868C treatment group. Serum concentrations of IFN-gamma in rats of BAYu3405 treatment group increased, but IL-4 and IL-5 decreased significantly when compared with those in rats of asthma group and BWA868C treatment group (P<0.01), and BALF EOS count was decreased significantly (P<0.01). Peripheral blood EOS count was higher than that in rats of normal control group, but was not significantly different from that in rats of asthma group and BWA868C treatment group. The combining capacity of CRTH2 and DP total combining capacity on EOS in asthma group, BAYu3405 treatment group and BWA868C treatment group were significantly higher than those in Group A (P<0.01). There was no significant difference in DP1 among all the groups (P>0.05).

CONCLUSIONCRTH2, but not DP1 antagonist can effectively ameliorate airway inflammation in rats with asthma.

Animals ; Asthma ; chemically induced ; drug therapy ; pathology ; Bronchi ; immunology ; pathology ; Carbazoles ; pharmacology ; therapeutic use ; Inflammation ; drug therapy ; Male ; Ovalbumin ; Prostaglandin D2 ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Immunologic ; antagonists & inhibitors ; Receptors, Prostaglandin ; antagonists & inhibitors ; Sulfonamides ; pharmacology ; therapeutic use

To explore the roles of regulatory peptides in the process of various anaphylactic inflammation of the airway, we observed the influence of four peptides, i.e., vasoactive intestinal peptide (VIP), epidermal growth factor (EGF), endothelin-1 (ET-1), and calcitonin gene-related peptide (CGRP), on the adhesion of eosinophil (EOS) to unstimulated and O(3)-stressed bronchial epithelial cells (BEC). From the experiments we observed that VIP and EGF decreased EOS adherence to O(3)-stressed BEC and downregulated airway inflammation; ET-1 and CGRP increased the adhesion of EOS to BEC in the inflammatory process; and CGRP aggravated O(3)-stressed reactions. The effects of ET-1 and CGRP were inhibited by W(7)and H(7). Anti-ICAM-1 antibody inhibited the adhesion of EOS to BEC, which brings to light that EOS adherence to BEC may be related to the expression of ICAM-1 of BEC.
Animals ; Antibodies ; pharmacology ; Bronchi ; cytology ; Cell Adhesion ; drug effects ; physiology ; Cells, Cultured ; Endothelin-1 ; pharmacology ; Eosinophils ; physiology ; Epidermal Growth Factor ; pharmacology ; Epithelial Cells ; physiology ; Female ; Intercellular Adhesion Molecule-1 ; immunology ; physiology ; Male ; Rabbits ; Vasoactive Intestinal Peptide ; pharmacology

Several studies have suggested the involvement of an autoimmune mechanism in aspirin (ASA)-intolerant asthma. To test this hypothesis, we measured the levels of circulating autoantibodies, such as IgG and IgA to tissue transglutaminase (TGase), IgG to cytokeratins (CKs) 8, 18, and 19, Clq-binding immune complex (CIC), and antinuclear antibody (ANA), in the sera of 79 patients with ASA-intolerant asthma (Group I) and those of two control groups, consisting of 61 patients with ASA-tolerant asthma (Group II) and 88 healthy control subjects (Group III) by means of ELISA. Significantly higher prevalences of IgG antibodies to CK18 (13.9%) and CK19 (17.7%) were noted in Group I, as compared with Group III (p<0.05 for all) not with Group II. Regarding the prevalences of other autoantibodies, the levels of ANA (1.3%), IgG to TGase (3.8%), and CIC (24.7%) in Group I were not significantly different from those in Groups II and III. Significant correlations were found between positivities for the anti-CK18 and anti-CK19 autoantibodies and the PC20 methacholine values in the analysis of asthma Groups I and II vs. normal controls, (p=0.001 and p=0.003, respectively). Further studies are needed to explore the potential involvement of an autoantibody-mediated mechanism in the clinical manifestation of bronchial asthma.
Middle Aged ; Male ; Keratins/chemistry ; Inflammation ; Humans ; Female ; *Drug Resistance ; Child ; Case-Control Studies ; Bronchi/*pathology ; Autoantibodies/*chemistry ; Asthma/*drug therapy/*immunology ; Aspirin/*pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Aged