Following allergen exposure, sensitized Brown-Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25+) in the airways. We tested the hypothesis that CD4+ T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)3, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by [3H]thymidine uptake. For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4+ and CD8+ T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50 x 10(6) total T cells, 20 x 10(6) and 5 x 10(6) CD4+ cells, and 5 x 10(6) CD8+ cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr, airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values PC100, PC200 and PC300) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline-injected donor rats (P
To evaluate the role of lymphocytes in the pathogenesis of allergic bronchoconstriction, we investigated whether allergic airway responses are adoptively transferred by antigen-primed lymphocytes in Brown Norway (BN) rats. Animals were actively sensitized to ovalbumin (OA) or sham sensitized, and 14 d later mononuclear cells (MNCs) were isolated from intrathoracic lymph nodes, passed through a nylon wool column, and transferred to naive syngeneic rats. Recipients were challenged with aerosolized OA or bovine serum albumin (BSA) (5% wt/vol) and analyzed for changes in lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), and bronchoalveolar lavage (BAL) cells. Recipients of MNCs from sensitized rats responded to OA inhalation and exhibited sustained increases in RL throughout the 8-h observation period, but without usual early airway responses. Recipients of sham-sensitized MNCs or BSA-challenged recipients failed to respond to antigen challenge. At 32 h after OA exposure, airway responsiveness to MCh was increased in four of seven rats that had received sensitized MNCs (p = 0.035). BAL eosinophils increased at 32 h in the recipients of both sensitized and sham-sensitized MNCs. However, eosinophil numbers in BAL were inversely correlated with airway responsiveness in the recipients of sensitized MNCs (r = -0.788, p = 0.036). OA-specific immunoglobulin E (IgE) was undetectable by enzyme-linked immunosorbent assay (ELISA) or passive cutaneous anaphylaxis (PCA) in recipient rats following adoptive transfer. In conclusion, allergic late airway responses (LAR) and cholinergic airway hyperresponsiveness, but not antigen-specific IgE and early responses, were adoptively transferred by antigen-primed lymphocytes in BN rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Airway inflammatory responses to specific inhalation challenges (SICs) with low-molecular-weight (LMW) and high-molecular-weight (HMW) agents have not been studied thoroughly. We assessed the changes in airway inflammatory cells following SIC in sensitized workers, and looked at the influence of various factors on the pattern of inflammatory responses to SIC.
Induced sputum analysis was performed in workers sensitized to LMW (n = 41) or HMW agents (n = 41) after a control day and after a positive SIC. Cell counts were compared with lung function and various clinical parameters.
In the LMW group, eosinophils were increased following late asthmatic responses (median [interquartile range], 0.02 [0.04] × 10(6) cells/g vs 0.30 [0.80] × 10(6) cells/g and 1.0% [3.5] vs 8.9% [8.0], P
Most, if not all, people are sensitized to mosquito bites in childhood. Cutaneous symptoms include immediate wheal-and-flare reactions and delayed bite papules, which tend to be more severe at the onset of the mosquito season. Systemic reactions to mosquito bites are, however, very rare. Recent immunoblot studies have demonstrated IgE antibodies to Aedes communis mosquito saliva 22 and 36 kD proteins. This confirms that specific sensitization occurs in man and indicates that mosquito-bite whealing is a classic type I allergic reaction. The delayed mosquito-bite papules seem to be cutaneous late-phase reactions mediated by eosinophils or they could also represent type IV lymphocyte-mediated immune reactions. People living in heavily infested areas such as Lapland frequently acquire tolerance to mosquito bites, and seem to have negligible levels of IgE but high amounts of IgG4 antisaliva antibodies. Desensitization treatment is a theoretical possibility but prophylactically given cetirizine, an H1-blocking antihistamine, has been shown to be helpful for people suffering from mosquito bites.
BACKGROUND: Bronchial hyperresponsiveness (BHR) is common in bakery workers. The relation between bronchial responsiveness measured with a tidal breathing method and smoking, airway symptoms, IgE-sensitization, nasal indices of inflammation and flour dust exposure have been studied with bronchial responsiveness expressed as a continuous outcome. MATERIAL AND METHODS: Bakery workers (n = 197) were subjected to interviews, questionnaires, allergy tests, workplace dust measurements and bronchial metacholine provocation. Eosinophil cationic protein (ECP) and alpha(2)-macroglobulin were measured in nasal lavage. Bronchial responsiveness was expressed as slope(conc), a measurement based on regressing the per cent reduction in FEV(1) at each provocation step. RESULTS: BHR expressed as slope(conc) was associated with smoking (P = 0.009), asthma symptoms at work (P = 0.001), and occupational IgE sensitization (P = 0.048). After adjusting for baseline lung function the association between BHR and IgE sensitization was no longer present. We demonstrated an association between nasal ECP and BHR (slope(conc)
Feeding a soluble antigen to an animal is known to cause a state of unresponsiveness against this antigen. If this antigen is given together with another antigen during the sensitization procedure, impairment of the response to the new antigen can also be seen, a phenomenon referred to as bystander suppression. The induction of tolerance against ovalbumin (OvA) and the effect of bystander suppression on the response to the hapten trimellitic anhydride (TMA), a cause of occupational asthma, were studied in Brown-Norway rats. Rats were fed either OvA-containing pellets or standard diet for 16 days before sensitization with the mixture of TMA and OvA. The animals were followed for 6 weeks after sensitization. Animals made tolerant to OvA showed a significantly suppressed delayed-type hypersensitivity (DTH) reaction against both OvA and TMA compared with the nontolerized control group at 5 weeks after sensitization, implying bystander suppression. By contrast, immunoglobulin (Ig)E and IgG antibody levels were suppressed only against OvA, whereas anti-TMA antibody levels were not affected. Airway eosinophilia after a single aerosol challenge at 6 weeks after sensitization using TMA conjugated to rat serum albumin, correlated with IgE anti-TMA levels in the group made tolerant to OvA and was not affected by OvA ingestion. In conclusion, suppressive factors released in ovalbumin-tolerant rats when they are challenged with ovalbumin, can suppress the response to trimellitic anhydride and this suppression is more pronounced for T-helper1-type responses.
CD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26- T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production.
We investigated the potential role of intercellular-adhesion molecule-1 (ICAM-1) in allergen-induced bronchial hyperresponsiveness (BHR) and inflammation in sensitised Brown-Norway rats. Rats were sensitised with ovalbumin (OA) intraperitoneally and 21 days later they were either exposed to 0.9% NaCl or 1% OA aerosol for 15 min. Rats exposed to OA aerosol were pretreated either with ICAM-1 antibody (3 mg/kg i.p. and i.v., 45 min prior to OA exposure) or with the diluent for the antibody. Eighteen to twenty-four hours after OA or 0.9% NaCl exposure, rats were anaesthetised, tracheostomised and mechanically ventilated, and airway responsiveness to acetylcholine (ACh) aerosol was measured as the provocative concentration of ACh needed to increase pulmorary resistance by 100% (PC100). Mean -log PC100 was increased in rats exposed to OA but pretreated with diluent (2.75 +/- 0.06) compared to rats treated with ICAM-1 antibody (2.51 +/- 0.08;
There are few longitudinal studies on health effects of dampness and moulds in workplace buildings. We studied associations between dampness and indoor moulds in workplace buildings and selected biomarkers as well as incidence and remission of sick building syndrome (SBS). The study was based on a ten-year prospective study (1992-2002) in a random sample of adults (N=429) from the Uppsala part of the European Community Respiratory Health Survey (ECRHS). The 10-year incidence (onset) of general, mucosal, dermal symptoms and any symptom improved when away from the workplace (work-related symptoms) was 7.2%, 11.6%, 6.4% and 9.4% respectively. The 10-year remission of general, mucosal, dermal symptoms and work-related symptoms was 71.4%, 57.1%, 70.4% and 72.2% respectively. Signs of dampness in the floor construction in any workplace building during follow up (cumulative exposure) was associated with incidence of mucosal symptoms (OR=2.43). Cumulative exposure to moldy odor was associated with incidence of work-related symptoms (OR=2.69). Cumulative exposure to dampness or moulds was associated with decreased remission of work-related symptoms (OR=0.20 for water leakage, OR=0.17 for floor dampness, and OR=0.17 for visible indoor mould growth). Working in a building repaired because of dampness (repaired building) or mould was associated with decreased remission of work-related symptoms (OR=0.32). Any dampness or moulds at baseline in the workplace building was associated with increased bronchial responsiveness (BR) and higher levels of Eosinphilic Cationic Protein (ECP) in serum and Eosinophilic counts in blood at baseline. Cumulative exposure to dampness and moulds, and work in a repaired building, was associated with increased BR at follow-up. In general, dampness and moulds in the workplace building is associated with increased incidence and decreased remission of SBS, as well as increased bronchial responsiveness and eosinophilic inflammation.