Influx of Neutrophils into the Airway Lumen at 4 h after Segmental Allergen Challenge in Asthma

Nocker, R. E. T.; Out, Theo A.; Weller, F. R.; Mul, Frederik P. J.; Jansen, Henk M.; Zee, Jaring S. van der

doi:10.1159/000024174

Cited by 60 publications

(63 citation statements)

References 21 publications

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“…During this phase, only the higher dose of S-CMC appeared effective. In asthma patients [27,28] and in animal models [15], neutrophils have been shown to be the first inflammatory cells in the airways after allergen challenge. Neutrophils are known to release several chemical mediators known to be toxic to the airways.…”

Section: Cytokine Levels In Cultured Cellsmentioning

confidence: 99%

S-carboxymethylcysteine normalises airway responsiveness in sensitised and challenged mice

Takeda

Miyahara

Kodama

et al. 2005

European Respiratory Journal

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S-carboxymethylcysteine (S-CMC) has been used as a mucoregulator in respiratory diseases. However, the mechanism of action of S-CMC on allergic airway inflammation has not yet been defined.In the present study, BALB/c mice were initially sensitised and challenged to ovalbumin (OVA) and, weeks later, re-challenged with OVA (secondary challenge). S-CMC (5-100 mg?kg -1 ) was administered from 2 days before the secondary challenge through to the day of assay. Mice developed airway hyperresponsiveness (AHR) 6 h after the secondary challenge and increased numbers of neutrophils were present in the bronchoalveolar lavage (BAL) fluid. At 72 h after secondary challenge, mice again developed AHR, but the BAL fluid contained large numbers of eosinophils. S-CMC treatment was found to reduce AHR and neutrophilia at 6 h, as well as eosinophilia and AHR at 72 h. These effects appeared to be dose dependent. Goblet cell hyperplasia, observed at 72 h, was reduced by S-CMC. In BAL fluid, increased levels of interferonc, interleukin (IL)-12 and IL-10 and decreased levels of IL-5 and IL-13 were detected.In conclusion, the data indicate that S-carboxymethylcysteine is effective in reducing airway hyperresponsiveness and airway inflammation at two distinct phases of the response to the secondary allergen challenge in sensitised mice.

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Section: Cytokine Levels In Cultured Cellsmentioning

confidence: 99%

S-carboxymethylcysteine normalises airway responsiveness in sensitised and challenged mice

Takeda

Miyahara

Kodama

et al. 2005

European Respiratory Journal

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“…Recruitment of neutrophils into the lungs is commonly seen in asthma and animal models of lung allergy (1)(2)(3)(4)(5). Mechanisms to explain increased neutrophil infiltration in asthma and allergy are not well characterized.…”

Section: Ag-specific Activation Of Cd4 ϩ T Cells As a Mechanism For Cmentioning

confidence: 99%

“…Consequently, it will be useful to understand the mechanisms explaining up-regulation of chemokines in lung allergy. It has recently been shown that segmental allergen challenge in allergic asthmatics rapidly induced neutrophil chemokine production and neutrophil influx (3). In that study, although neutrophil chemokine production was thought to be mast cell independent, the underlying mechanism was unclear.…”

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confidence: 92%

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Rapid Up-Regulation of CXC Chemokines in the Airways after Ag-Specific CD4+ T Cell Activation

Knott

Gater

Dunford

et al. 2001

The Journal of Immunology

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Ag-specific activation of CD4+ T cells is known to be causative for the cytokine production associated with lung allergy. Chemokine-induced leukocyte recruitment potentially represents a critical early event in Ag-induced lung inflammation. Whether Ag-specific, lung CD4+ T cell activation is important in lung chemokine production is currently not clear. Using αβ-TCR transgenic BALB/c DO11.10 mice, we investigated the ability of Ag-specific CD4+ T cell activation to induce lung chemokine production and leukocyte recruitment. Within 1 h of exposure of DO11.10 mice to OVA aerosol, lung mRNA and protein for the neutrophil chemokines KC and macrophage inflammatory protein (MIP)-2 were greatly increased. Accordingly, neutrophils in the airways increased by >50-fold, and KC and MIP-2 proved to be functional because their neutralization significantly reduced airway neutrophilia. CD4+ T cell activation was critical because CD4+ but not CD8+ T cell depletion reduced KC production, which correlated well with the previously observed inhibition of neutrophil influx after CD4+ T cell depletion. In vitro studies confirmed that OVA-induced KC and MIP-2 production was conditional upon the interaction of CD4+ T cells with APCs. A likely secondary mediator was TNF-α, and a probable source of these chemokines in the lung was alveolar macrophages. Thus, Ag-specific CD4+ T cell activation in the lung leads to rapid up-regulation of neutrophil chemokines and the recruitment of neutrophils to the site of Ag exposure. This may be a key early event in the pathogenesis of Ag-induced lung inflammation.

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“…CCL11/eotaxin [6]), is broadly accepted as critical to the eosinophil response. However, CXCL8/interleukin (IL)-8 is also strongly expressed within allergic lesions [7][8][9][10] and eosinophils are responsive to this CXCR1/CXCR2 ligand [11,12]. Indeed, the decreased eosinophilia after allergen immunotherapy may be related to reduced CXCL8/IL-8 responses to allergen challenge [13].…”

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confidence: 99%

Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response

Gordon

Swystun²,

Li³

et al. 2003

Eur Respir J

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Regular salbutamol use can exacerbate allergen-induced airway eosinophilia in asthmatics, but its effect on airway eosinophil chemokine responses is unknown.Asthmatic subjects (n=14) were treated for 10 days with placebo or salbutamol in a double-blind, cross-over study, then given same-dose allergen challenges. Their sputa were then analysed 1 and 7 h later for a panel of eosinophil-related cytokines. Eosinophils from five test and three control subjects were tested for expression of CXCL8/interleukin (IL)-8, and its receptors and responsiveness to CCL11/eotaxin and CXCL8/IL-8.Sputum CXCL8/IL-8, but not IL-5, CCL5/regulated on activation, T-cell expressed and secreted, CCL7/monocyte chemotactic protein-3, CCL11/eotaxin, granulocytemacrophage colony-stimulating factor or tumour necrosis factor levels, were increased (42%) by the salbutamol treatments. The CXCL8/IL-8 levels correlated with the proportions of sputum eosinophils and these cells, but not other sputum cells, stained strongly for CXCL8/IL-8. The circulating eosinophils of the tested subjects (n=5) expressed CXCL8/IL-8 receptors and secreted high levels of this chemokine. Neutralisation of sputum CXCL8/IL-8 reduced eosinophil chemotactic responses to these samples by 19¡5%.These data suggest that regular use of salbutamol can augment airway CXCL8/ interleukin-8 responses to allergen challenge and that this CXCL8/interleukin-8 could contribute to the airway inflammatory response. Eur Respir J 2003; 22: 118-126 Inhaled b 2 -adrenergic receptor agonists (b 2 -agonists) comprise a primary therapy for bronchoconstriction in allergic asthma patients. However, evidence suggests that regular use of b 2 -agonists can reduce their effectiveness [1, 2] and lead to increased airway hyperresponsiveness [3][4][5] and eosinophil/ mast cell responses [4,5] to allergen challenge. Given the association of eosinophils with asthma severity and pathology [6], the cellular mechanisms that may regulate this eosinophil response were questioned.Eosinophils express receptors for many molecules that are highly pertinent to asthma pathophysiology [6]. For example, the CCR3 receptor, which binds multiple CC chemokines (e.g. CCL11/eotaxin [6]), is broadly accepted as critical to the eosinophil response. However, CXCL8/interleukin (IL)-8 is also strongly expressed within allergic lesions [7][8][9][10] and eosinophils are responsive to this CXCR1/CXCR2 ligand [11,12]. Indeed, the decreased eosinophilia after allergen immunotherapy may be related to reduced CXCL8/IL-8 responses to allergen challenge [13].In a recent study in which mildly asthmatic subjects (n=14) regularly used salbutamol (or placebo) for 10 days, an exacerbation of asthmatic responses (forced expiratory volume in one second (FEV1), serum tryptase and sputum eosinophils) to allergen challenge was observed [5]. In order to gain insight into potential mechanisms behind this eosinophilia [4,5], a panel of nine pertinent eosinophil-signalling cytokines/ chemokines in sputum, previously obtained from these subjec...

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Influx of Neutrophils into the Airway Lumen at 4 h after Segmental Allergen Challenge in Asthma

Cited by 60 publications

References 21 publications

S-carboxymethylcysteine normalises airway responsiveness in sensitised and challenged mice

S-carboxymethylcysteine normalises airway responsiveness in sensitised and challenged mice

Rapid Up-Regulation of CXC Chemokines in the Airways after Ag-Specific CD4+ T Cell Activation

Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response

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