Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis

Gibson, Peter G.; Wark, Peter; Simpson, Jodie L.; Meldrum, Catherine A.; Meldrum, Suzanne; Saltos, Nicholas; Boyle, M

doi:10.1183/09031936.03.00001803

Cited by 63 publications

(39 citation statements)

References 34 publications

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“…There is a robust correlation between airway neutrophils and human asthma (recently reviewed in Ref. 53): the severity of airway disease appears to correlate with number of neutrophils in the airway in both asthma (54) and allergic bronchopulmonary aspergillosis (8,25), and neutrophils are overrepresented in patients with asthma exacerbations, severe or poorly controlled asthma, and in those who die of asthma (9,11,(55)(56)(57)(58)(59)(60). In the context of this strong association noted in human disease, our study found long-term elevation in lung neutrophils in a mouse model of chronic airway allergy to clinically relevant Ags of a ubiquitous environmental mold.…”

Section: Discussionmentioning

confidence: 99%

“…The association of neutrophil presence and MMP-9 activity is recognized in human airway allergy (25,70,71) and MMP-9 deficiency affects airway responses in mouse models of airway allergy (44 -47, 72, 73). Importantly, while our results underline the relevance of neutrophil-derived MMP-9 in airway inflammation, they do not preclude a role for other cellular sources of this enzyme in the context of allergy; indeed, our results indicate that MMP-9 activity in the lungs is substantially reduced, but not completely ablated, in the absence of neutrophils.…”

Section: Figure 10mentioning

confidence: 99%

“…This organism is also an important cause of allergic airways disease, including in a subset of cases of human asthma (22) and a distinct clinical entity, allergic bronchopulmonary aspergillosis (23,24). Tissue neutrophil accumulation correlates with disease severity in patients with allergic airways disease to Aspergillus (7,8,25), but its role in disease pathogenesis is not known.…”

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confidence: 99%

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Neutrophils Regulate Airway Responses in a Model of Fungal Allergic Airways Disease

Park

Wiekowski²,

Lira

et al. 2006

The Journal of Immunology

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Neutrophils infiltrate airway walls in patients with allergic airway diseases and in animal models of these illnesses, but their contribution to the pathogenesis of airway allergy is not established. We hypothesized that, in a mouse model of airway allergy to the ubiquitous environmental mold, Aspergillus fumigatus, airway neutrophils contribute to disease severity. Ab-mediated neutrophil depletion resulted in reduced airway hyperresponsiveness and remodeling, whereas conditional transgenic overexpression of the neutrophil chemotactic molecule, CXCL1, in airway walls resulted in worsened allergic responses. This worsened phenotype was associated with a marked increase in the number of airway neutrophils but not other lung leukocytes, including eosinophils and lymphocyte subsets, and depletion of neutrophils in sensitized mice with transgenic overexpression of CXCL1 resulted in attenuated airway responses. The number of lung neutrophils correlated with lung matrix metalloproteinase 9 (MMP-9) activity both in the context of neutrophil depletion and with augmented neutrophil recruitment to the airways. Although wild-type and MMP-9-deficient neutrophils homed to the inflamed airways to a similar extent, transfer of wild-type, but not MMP-9-deficient, neutrophils to MMP-9-deficient animals resulted in augmented allergic airway responses. Taken together, these data implicate neutrophils in the pathogenesis of fungal allergic airway disease.

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Section: Discussionmentioning

confidence: 99%

Section: Figure 10mentioning

confidence: 99%

mentioning

confidence: 99%

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Neutrophils Regulate Airway Responses in a Model of Fungal Allergic Airways Disease

Park

Wiekowski²,

Lira

et al. 2006

The Journal of Immunology

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“…The costimulatory molecule OX40 ligand has been found to be important in Th2 inflammatory responses in patients with ABPA associated with cystic fibrosis, with increased Th2 activity inversely correlating with circulating vitamin D levels (88). Proteolytic enzymes and mycotoxins from Aspergillus in colonized airways, along with eosinophilic inflammation and neutrophilic inflammation, may cause the characteristic central bronchiectasis seen in many cases of ABPA (50).…”

Section: Abpamentioning

confidence: 99%

Eosinophilic Pneumonias

2012

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SUMMARY This review starts with discussions of several infectious causes of eosinophilic pneumonia, which are almost exclusively parasitic in nature. Pulmonary infections due specifically to Ascaris , hookworms, Strongyloides , Paragonimus , filariasis, and Toxocara are considered in detail. The discussion then moves to noninfectious causes of eosinophilic pulmonary infiltration, including allergic sensitization to Aspergillus , acute and chronic eosinophilic pneumonias, Churg-Strauss syndrome, hypereosinophilic syndromes, and pulmonary eosinophilia due to exposure to specific medications or toxins.

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“…Aspergillus fumigatus, which induces allergic bronchopulmonary aspergillosis (ABPA) in 25% of severe asthmatics, is one of the most common fungi involved (1,2). Neutrophilic airway inflammation is now well recognized as being a feature of severe asthma (3)(4)(5) and ABPA (6,7). During acute infection, neutrophils are crucial for antifungal defense (8,9), and lack of neutrophils is the best appreciated risk factor for invasive aspergillosis (10).…”

Section: Th17 | Tolerancementioning

confidence: 99%

TNF-α from inflammatory dendritic cells (DCs) regulates lung IL-17A/IL-5 levels and neutrophilia versus eosinophilia during persistent fungal infection

Fei

Bhatia

Oriss

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

116

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Aspergillus fumigatus is commonly associated with allergic bronchopulmonary aspergillosis in patients with severe asthma in which chronic airway neutrophilia predicts a poor outcome. We were able to recapitulate fungus-induced neutrophilic airway inflammation in a mouse model in our efforts to understand the underlying mechanisms. However, neutrophilia occurred in a mouse strain-selective fashion, providing us with an opportunity to perform a comparative study to elucidate the mechanisms involved. Here we show that TNF-α, largely produced by Ly6c + CD11b + dendritic cells (DCs), plays a central role in promoting IL-17A from CD4 +

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Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis

Cited by 63 publications

References 34 publications

Neutrophils Regulate Airway Responses in a Model of Fungal Allergic Airways Disease

Neutrophils Regulate Airway Responses in a Model of Fungal Allergic Airways Disease

Eosinophilic Pneumonias

TNF-α from inflammatory dendritic cells (DCs) regulates lung IL-17A/IL-5 levels and neutrophilia versus eosinophilia during persistent fungal infection

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