Inflammatory determinants of asthma severity: Mediator and cellular changes in bronchoalveolar lavage fluid of patients with severe asthma☆☆☆★

Virchow, J. Christian; Kroegel, Claus; Walker, Christoph; Matthys, H

doi:10.1016/s0091-6749(96)70014-3

Cited by 78 publications

(30 citation statements)

References 20 publications

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“…However, allergic sensitization cannot be detected in a significant number of adult patients with asthma (1-3). Nonallergic asthma usually begins at an older age and is clinically more severe than allergic asthma (3)(4)(5). Nonallergic asthma has been referred to as "intrinsic asthma" on the basis of a belief that there must be an etiologic agent in the patient's own body (3).…”

mentioning

confidence: 99%

Identification of Cytokeratin 18 as a Bronchial Epithelial Autoantigen Associated with Nonallergic Asthma

Nahm

Lee

Yim

et al. 2002

Am J Respir Crit Care Med

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The allergic response to common environmental agents (allergens) has been regarded as an important mechanism in the development of airway inflammation of patients with asthma. However, allergic sensitization cannot be detected in a significant number of adult patients with asthma. The etiologic mechanism responsible for nonallergic asthma has not yet been identified. The idea of a possible involvement of autoimmunity in the pathogenesis of nonallergic asthma has been proposed by earlier studies. To test for the possible presence of an autoimmune response to bronchial epithelial cell antigens in nonallergic asthma, we examined circulating autoantibodies to cultured human bronchial epithelial cells (BEAS-2B) in sera from patients with nonallergic asthma by immunoblot analysis. IgG autoantibodies to the 49-kD bronchial epithelial cell antigen were detected in 10 of 23 patients with nonallergic asthma (43%), 3 of 27 patients with allergic asthma (11%), 2 of 20 patients with systemic lupus erythematosus (10%), and 3 of 34 healthy volunteers (9%) (p Ͻ 0.005). The 49-kD autoantigen was purified and identified as cytokeratin 18 by amino acid sequencing. In this study, we identified cytokeratin 18 as a bronchial epithelial autoantigen associated with nonallergic asthma. Further studies are needed to determine the significance of autoimmunity in nonallergic asthma.

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confidence: 99%

Identification of Cytokeratin 18 as a Bronchial Epithelial Autoantigen Associated with Nonallergic Asthma

Nahm

Lee

Yim

et al. 2002

Am J Respir Crit Care Med

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“…Elevated levels of GM-CSF have been well described in bronchoalveolar lavage, endobronchial biopsy, and sputum samples from asthmatics (1,(7)(8)(9)(10)(11)(12). Elevated levels of GM-CSF, largely derived from epithelial cells, have been demonstrated to increase eosinophil activation and survival in asthmatics (13)(14)(15).…”

mentioning

confidence: 99%

Regulation of Expression of Granulocyte-Macrophage Colony-Stimulating Factor in Human Bronchial Epithelial Cells: Roles of Protein Kinase C and Mitogen-Activated Protein Kinases

Reibman

Talbot

Hsu

et al. 2000

The Journal of Immunology

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GM-CSF has a major role in the immune and inflammatory milieu of the airway. Airway epithelial cells (AEC) are among the first targets of environmental stimuli and local cytokines, in response to which they can produce GM-CSF. The regulation of GM-CSF is only minimally understood in AEC. We hypothesized that GM-CSF expression in AEC would result from activation of protein kinase C (PKC) and subsequent activation of the extracellular signal-regulated kinase (MAPKerk1/2) pathway, so we investigated signal transduction pathways in human primary culture bronchial epithelial cells (HBECs). TNF-α, IL-1β, and PMA induced the release of GM-CSF in HBECs. The robust response to PMA was not detected in SV40 adenovirus-transformed normal human bronchial epithelial cells (BEAS-2B). PMA and TNF-α stimulation of GM-CSF required activation of PKC (inhibition by staurosporine and bisindolylmaleimide I). GM-CSF expression was up-regulated by a nonphorbol PKC activator, but not by an inactive PMA analogue. PMA-induced GM-CSF production in HBECs did not require a Ca2+ ionophore and was not inhibited by cyclosporin A. Activation of MAPKerk1/2 via PKC was associated with and was required for GM-CSF production induced by PMA and TNF-α. The data demonstrate regulation of GM-CSF in HBECs by PKC pathways converging on the MAPKerk1/2 pathway and further define cell-specific regulation critical for local airway responses.

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“…LPR is thought to be a more essential component in the pathogenesis of allergic diseases than EPR because of its correlation with the severity of these diseases and also with the results in clinical trials of antiallergic drugs (19,20). A high (100 mg / kg), but not a low (5 mg / kg), dose of DSCG suppressed both EPR and LPR (Figs.…”

Section: Discussionmentioning

confidence: 94%

A Late Cutaneous Response in Actively Sensitized Rats: a New Method for Evaluating the Efficacy of Antiallergic Drugs

et al. 2006

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Abstract. We established a new and facile model to investigate allergic mechanism and assess the effect of antiallergic compounds. Male Wistar rats were actively or passively sensitized. Active sensitization was performed by injection of both dinitrophenylated-ovalbumin (DNP-OA) and Bordetella pertussis. Nine days later, DNP-OA was injected into the right hind footpad. This antigen challenge induced a biphasic footpad swelling that consisted of an early-phase (EPR) and a late-phase response (LPR). In rats passively sensitized with rat anti-DNP-OA serum, DNP-OA induced only EPR. The EPR was suppressed by disodium cromoglycate, a mast cell stabilizer, but not by cyclosporin A, an immunosuppressant, while the LPR was suppressed by cyclosporin A. Furthermore, to investigate these two allergic responses determined by the interactions between the hapten and the carrier proteins, two distinct haptenated antigens were created. DNP-Ascaris (DNP-As) induced a marked EPR and LPR in DNP-As-sensitized rats. However, DNP-As induced only EPR in DNP-OA-sensitized rats, indicating that the usage of the same carrier protein in both sensitization and challenge was necessary for induction of LPR. These data suggest that this actively sensitization model in which EPR and LPR are functionally distinguishable should be useful for evaluating the efficacy of antiallergic compounds.

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Inflammatory determinants of asthma severity: Mediator and cellular changes in bronchoalveolar lavage fluid of patients with severe asthma☆☆☆★

Cited by 78 publications

References 20 publications

Identification of Cytokeratin 18 as a Bronchial Epithelial Autoantigen Associated with Nonallergic Asthma

Identification of Cytokeratin 18 as a Bronchial Epithelial Autoantigen Associated with Nonallergic Asthma

Regulation of Expression of Granulocyte-Macrophage Colony-Stimulating Factor in Human Bronchial Epithelial Cells: Roles of Protein Kinase C and Mitogen-Activated Protein Kinases

A Late Cutaneous Response in Actively Sensitized Rats: a New Method for Evaluating the Efficacy of Antiallergic Drugs

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