(1/1001) Prolonged eosinophil accumulation in allergic lung interstitium of ICAM-2 deficient mice results in extended hyperresponsiveness.

ICAM-2-deficient mice exhibit prolonged accumulation of eosinophils in lung interstitium concomitant with a delayed increase in eosinophil numbers in the airway lumen during the development of allergic lung inflammation. The ICAM-2-dependent increased and prolonged accumulation of eosinophils in lung interstitium results in prolonged, heightened airway hyperresponsiveness. These findings reveal an essential role for ICAM-2 in the development of the inflammatory and respiratory components of allergic lung disease. This phenotype is caused by the lack of ICAM-2 expression on non-hematopoietic cells. ICAM-2 deficiency on endothelial cells causes reduced eosinophil transmigration in vitro. ICAM-2 is not essential for lymphocyte homing or the development of leukocytes, with the exception of megakaryocyte progenitors, which are significantly reduced.  (+info)

(2/1001) Nasal nitric oxide concentration in paranasal sinus inflammatory diseases.

In normal upper airways, nitric oxide is generated by the paranasal sinus epithelium and then diffuses into the nasal cavities. This study examined whether or not nasal NO concentration is affected by paranasal sinus inflammatory diseases. The influence of obstruction (nasal polyposis) and/or inflammation (allergy or chronic sinusitis) of the paranasal sinuses on nasal NO concentration was evaluated in nasal allergic (n=7 patients) or nonallergic (n=20) polyposis, nonallergic chronic sinusitis (n=10) and Kartagener's syndrome (n=6) and compared with control subjects (n=42). A score of alteration of the paranasal sinus (number of altered and occluded sinuses) was determined by a computed tomography scan. The nasal NO concentration in nasal nonallergic polyposis (150+/-20 parts per billion (ppb)) was significantly decreased compared with both controls (223+/-6 ppb, p=0.01) and polyposis with allergy (272+/-28 ppb, p<0.0001). In each group, the nasal NO concentration was inversely correlated with the extent of tomodensitometric alteration of the paranasal sinuses. In Kartagener's syndrome, the nasal NO concentration (14+/-2 ppb) was drastically decreased compared with all other groups, despite the presence of open paranasal sinuses. Thus, the nasal NO concentration in patients with nasal polyposis appeared to be dependent on both the allergic status and the degree of obstruction of the paranasal sinuses.  (+info)

(3/1001) Expression of heat shock protein 72 by alveolar macrophages in hypersensitivity pneumonitis.

The current study was done to look at a possible role of heat shock proteins (HSPs) in hypersensitivity pneumonitis (HP). The specific aims were to determine whether there was a difference in the expression of HSP72 in alveolar macrophages (AMs) between mice challenged with HP antigen and saline-treated control mice and between AMs obtained by bronchoalveolar lavage from 18 patients with HP and 11 normal subjects. The expression of HSP72 was studied under basal conditions and under a mild heat shock. HSP72 expression by AMs in response to in vitro stimulation with Saccharopolyspora rectivirgula was lower in AMs of control mice than in those of HP animals. HSP72 was constitutively expressed in AMs of both normal and HP subjects. Densitometric ratios showed that AMs from normal subjects responded to heat shock with a 39 degrees C-to-37 degrees C ratio of 1.72 +/- 0.18 (mean +/- SE), and AMs from HP patients responded with a ratio of 1.16 +/- 0.16 (P = 0.0377). This decreased induction by additional stress of AMs could lead to an altered immunoregulatory activity and account for the inflammation seen in HP.  (+info)

(4/1001) An adoptive transfer model of allergic lung inflammation in mice is mediated by CD4+CD62LlowCD25+ T cells.

Animal models of allergic lung inflammation have provided important insight into the cellular and biochemical factors involved in the pathogenesis of human asthma. Herein, we describe an adoptive transfer model of OVA-specific eosinophilic lung inflammation in the mouse that is used to characterize the cells involved in mediating the pulmonary inflammatory response. We report that freshly isolated spleen cells from OVA-sensitized mice are unable to prime naive recipient mice to respond to a subsequent OVA aerosol challenge. Subjecting the spleen cells to short term restimulation with Ag in vitro, however, renders the cells competent to transfer activity. The magnitude and the kinetics of the eosinophilic pulmonary inflammation in the adoptive transfer recipients are nearly identical with those generated by a more conventional active sensitization/challenge protocol, with the notable exception of differential production of plasma IgE in the two models. Extensive negative and positive selection of splenocyte subtypes indicates that the transfer of Ag-primed CD4+ T cells is both necessary and sufficient to establish full responsiveness in the recipient mice. Additional phenotypic characterization of the transfer-reactive CD4+ T cells indicates that they are found within the CD62LlowCD25+ subset and secrete high levels of IL-5 in response to Ag stimulation. Limiting dilution analysis-derived minimal frequency estimates indicate that approximately 1 in 8500 of the sensitized, cultured spleen cells produces IL-5 in response to OVA stimulation in vitro, suggesting that eosinophilic lung inflammation can be induced in naive mice by the transfer of <1200 Ag-specific CD4+ T cells.  (+info)

(5/1001) Down-regulation of human basophil IgE and FC epsilon RI alpha surface densities and mediator release by anti-IgE-infusions is reversible in vitro and in vivo.

Previously, infusions of an anti-IgE mAb (rhumAb-E25) in subjects decreased serum IgE levels, basophil IgE and FcepsilonRIalpha surface density, and polyclonal anti-IgE and Ag-induced basophil histamine release responses. We hypothesized that these effects would be reversed in vivo by discontinuation of infusions and in vitro by exposing basophils to IgE. Subjects received rhumAb-E25 biweekly for 46 wk. Blood samples taken 0-52 wk after rhumAb-E25 were analyzed for serum IgE and basophil expression of IgE, FcepsilonRIalpha, and CD32. Basophil numbers were unaffected by infusions. Eight weeks after infusions, free IgE levels rose in vivo but did not reach baseline. Basophil IgE and FcepsilonRIalpha rose in parallel with free IgE while CD32 was stable. FcepsilonRI densities, measured by acid elution, returned to 80% of baseline, whereas histamine release responses returned to baseline. Basophils cultured with or without IgE or IgG were analyzed for expression of IgE, FcepsilonRIalpha, and CD32. By 7 days with IgE, expression of IgE and FcepsilonRIalpha rose significantly, whereas cultures without IgE declined. IgE culture did not effect CD32. IgG culture did not effect expression of any marker. The present results strongly suggest that free IgE levels regulate FcepsilonRIalpha expression on basophils.  (+info)

(6/1001) Bakery work, atopy and the incidence of self-reported hay fever and rhinitis.

The aims of this study were to estimate the risk to bakers of developing hay fever and rhinitis, to assess the modifying effect of atopy and to estimate the occurrence of job change due to nasal symptoms. A retrospective cohort study was performed among bakers trained in Swedish trade schools from 1961 to 1989 (n=2,923). School control subjects (n=1,258) comprised students in other programmes in the trade schools and population controls (n=1,258) were randomly selected from the general population. A questionnaire on hay fever, rhinitis, the year of onset of these diseases, change of work due to nasal symptoms and work history was mailed to all participants. The atopic state of the responders was assessed by questions on allergic diseases in childhood and among next of kin. Incidence rates for hay fever and other rhinitis were calculated. The relative risk (RR) for hay fever when working as a baker compared with all control subjects combined was increased in males (RR=1.9, 95% confidence interval (CI) 1.2-2.9). The RR for rhinitis in male bakers compared with combined control subjects was 2.8 (95% CI 2.3-3.4) and for female bakers 2.0 (1.6-2.7). Of the bakers, 6.1% had changed job due to nasal symptoms, significantly more than the controls. A history of respiratory atopy increased the incidence rates of hay fever and rhinitis, with a synergistic effect between atopy and bakery work in males. In conclusion, Swedish bakers, mainly working in the 1970s and 1980s, had an approximately doubled risk of developing rhinitis. Male bakers also had an increased risk for hay fever. There was a synergistic effect of bakery work and atopy such as a family history of hay fever. Bakers also changed job due to nasal symptoms more often than control subjects.  (+info)

(7/1001) Altered contractile sensitivity of isolated bronchial artery to phenylephrine in ovalbumin-sensitized rabbits.

We tested the hypothesis that atopy and/or allergic lung inflammation enhances alpha1-adrenoceptor-mediated contractions of the bronchial artery. Bronchial arterial resistance vessels were isolated from rabbits that had undergone either systemic ovalbumin (OVA) sensitization followed by saline aerosol challenge (OVA/saline rabbits), or OVA sensitization followed by OVA aerosol challenge (OVA/OVA rabbits), or no sensitization followed by saline aerosol challenge (control rabbits). In OVA/OVA rabbits, bronchoalveolar lavage and lung histology revealed lymphocytic and eosinophilic inflammation. Arterial rings were contracted with phenylephrine (PE). In endothelium-intact arteries isolated from OVA/saline and OVA/OVA rabbits, PE responsiveness was enhanced compared with that of arteries isolated from controls. The nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester increased the contractile response to PE in all three experimental groups to a similar degree, suggesting that depressed NOS activity was not involved in the enhanced PE responsiveness in OVA/saline and OVA/OVA rabbits. After endothelium removal, arteries from OVA/saline and control rabbits showed similar PE responsiveness, indicating that the enhancement of PE responsiveness was endothelium dependent, possibly due to an endothelial constricting factor. In OVA/OVA rabbits, endothelium-denuded arteries showed decreased PE responsiveness compared with the other two groups; this difference was abolished by NG-nitro-L-arginine methyl ester. We conclude that systemic sensitization with OVA per se enhances PE-induced contractions of isolated bronchial arteries in rabbits by an endothelium-dependent mechanism and that allergic lung inflammation attenuates this effect by increased nonendothelial NOS activity.  (+info)

(8/1001) Stem cell factor-induced airway hyperreactivity in allergic and normal mice.

The induction of airway hyperreactivity during allergic responses involves multiple ill-defined mechanisms. Recently a role for stem cell factor (SCF) in the development of allergic eosinophilic airway inflammation has been identified. In the present study we demonstrate that SCF has a role in both the inflammatory response and airway hyperreactivity. Neutralization of SCF or examination of SCF-mutant mice, which were deficient in SCF and pulmonary mast cells, demonstrated significant alterations in the allergen-induced airway hyperreactive responses. The reduced hyperreactivity response was accompanied by a significant reduction in eosinophil accumulation. To examine the direct role of SCF on airway hyperreactivity, we administered SCF into the airways of normal mice via intratracheal injections and demonstrated a dose dependent increase in airway hyperreactivity at 4 hours that was maintained at 24 hours after administration. Instillation of SCF into SCF-deficient (mast cell deficient) mice demonstrated significantly lower increases in airway hyperreactivity compared with the littermate controls with normal mast cell numbers. These studies demonstrate that locally expressed SCF can induce changes in airway physiology via mast cell activation, verifying the role of SCF in allergic airway inflammation and hyperreactivity.  (+info)