Neutrophils in asthma pathophysiology

Ennis, Madeleine

doi:10.1007/s11882-003-0029-2

Cited by 70 publications

(55 citation statements)

References 72 publications

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“…Neutrophils have been suggested to play a role during the acute exacerbation of asthma (24). Interestingly and in addition to CCL11, patients with asthma had elevated levels of CXCL8 and neutrophils in sputum and there was a positive correlation between these two variables.…”

Section: Discussionmentioning

confidence: 96%

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation

Daldegan

Teixeira

Talvani

2005

Braz J Med Biol Res

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Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory illnesses characterized by chronic inflammation of the airways. The characterization of induced or spontaneously produced sputum is a useful technique to assess airway inflammation. In the present study, we compared the concentrations of CCL2, CCL11, CXCL8, and tumor necrosis factor-α (TNF-α) in plasma and induced sputum of patients with severe asthma or COPD and correlated the levels of these mediators with inflammatory cells in sputum. Asthmatic patients had elevated levels of eosinophils (40.1 ± 6.24%) in sputum whereas neutrophils (63.3 ± 4.66%) predominated in COPD patients. The levels of the chemokine CCL11 were markedly increased in sputum (708.7 ± 330.7 pg/ml) and plasma (716.6 ± 162.2 pg/ml) of asthmatic patients and correlated with the percentage of eosinophils in induced sputum. The concentrations of CXCL8 (817.0 ± 105.2 pg/ml) and TNF-α (308.8 ± 96.1 pg/ml) were higher in sputum of COPD patients and correlated with the percentage of neutrophils in induced sputum. There was also an increase in the concentrations of CXCL8 (43.2 ± 6.8 pg/ml) in sputum of asthmatic patients. These results validate that sputum is a suitable method to assess chemokines and cytokines associated with asthma and COPD. Moreover, the mechanisms involved in the synthesis of CCL11 and CXCL8/TNF-α would be helpful to better understand the inflammatory profile associated with asthma and COPD, respectively.

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Section: Discussionmentioning

confidence: 96%

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation

Daldegan

Teixeira

Talvani

2005

Braz J Med Biol Res

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“…41,42). In such conditions, it has been proposed that activated neutrophils release free radicals, inflammatory mediators, and proteases that can damage lung tissue, leading to flooding of alveoli by plasma liquid and proteins.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

Tate

Deng

Jones

et al. 2009

The Journal of Immunology

286

308

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The clinical response to influenza infection ranges from mild disease to severe pneumonia and it remains unclear whether the inflammatory response to infection is protective or pathogenic. We have defined a novel role for neutrophils in ameliorating lung injury during influenza infection, thereby limiting development of severe disease. Infection of neutrophil-depleted mice with influenza virus HKx31 (H3N2) led to rapid weight loss, pneumonia, and death. Neutropenia was associated with enhanced virus replication in the respiratory tract; however, viral titers were declining at the time of death, leading us to investigate other factors contributing to mortality. In addition to thymic atrophy, lymphopenia, and viremic spread, depletion of neutrophils led to exacerbated pulmonary inflammation, edema, and respiratory dysfunction. Thus, while it is well established that neutrophils contribute to lung injury in a range of pathological conditions, reduced numbers or impaired neutrophil function can facilitate progression of mild influenza to severe clinical disease.

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“…The extent to which such mast cell-dependent mechanisms may influence the expression of IL-17-dependent immune responses in other settings remains to be determined, and may well vary according to the particular biological response examined. However, it is worth mentioning here that work in human subjects both has suggested that neutrophils may be potentially important contributors to airway pathology in certain subsets of patients with asthma, [41][42][43][44][45][46][47][48] and has identified IL-17 expression in the lungs of some subjects with this disorder. 32,[49][50][51][52][53] Therefore, it will be of interest to attempt to investigate whether the mechanisms that contribute to the mast cell-dependent enhancement of IL-17-dependent airway neutrophilia that have been revealed in our analyses of OTII mice have any bearing on the regulation of neutrophil recruitment that can occur in human asthma.…”

Section: Discussionmentioning

confidence: 99%

Mast cell–derived TNF can promote Th17 cell–dependent neutrophil recruitment in ovalbumin-challenged OTII mice

Nakae

Suto

Berry

et al. 2006

Blood

144

124

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IntroductionSeveral proinflammatory cytokines, including TNF, IL-1, and IL-17, can directly induce neutrophil recruitment. For example, inhalation of recombinant TNF, IL-1, or IL-17 can provoke neutrophil infiltration into the airways. [1][2][3] These cytokines can also play important roles in the pulmonary neutrophilia induced by infection with the Gram-negative bacteria Klebsiella pneumoniae, and can contribute to bacterial clearance. [4][5][6] However, both the roles of these proinflammatory cytokines, and the most important cellular sources of their production, can vary according to the models of inflammation analyzed. For example, in mice, mast cell-derived TNF has been reported to contribute importantly to neutrophil recruitment and host defense against K. pneumoniae. 7 By contrast, it has been reported that 8,9 but neither TNF nor IL-1, 10 is important for the pulmonary neutrophilia induced by LPS, a component of Gram-negative bacteria.To date, no reports have investigated the possible role of mast cells in the development of T helper 17 (Th17) cell-dependent, neutrophil-rich inflammatory responses, either in the airways or in other anatomical sites. To address this question, we decided to use a model of protein antigen (Ag) (ovalbumin [OVA])-induced neutrophil-predominant airway inflammation in OVA-specific T-cell receptor (TCR)-expressing mice. We took this approach because of reports indicating that OVA challenge can induce neutrophil-rich airway inflammation in OVA-specific TCR-expressing BALB/c-DO11.10 mice, 11,12 and that IL-17 is required for the induction of airway hyperreactivity (AHR) in this model. 13 However, we elected to use OVA-specific TCR-expressing C57BL/6-OTII mice, 14 instead of BALB/c-DO11.10 mice, for the work reported herein. C57BL/6-OTII mice are on the same strain background as mice that are either profoundly deficient in mast cells, lack the FcR␥ chain (that is required for the activation of mast cells via either the Fc⑀RI or Fc␥RIII that are expressed on their surface 15,16 ), or lack IL-17 or any of several other specific cytokines or cytokine receptors. Therefore, by working with C57BL/6-OTII mice, we were able to use a genetic approach to investigate in detail the importance of each of these candidate elements in the airway neutrophil infiltration elicited by OVA challenge in this model. Materials and methods Experimental approachWe first established and characterized a model of OVA-induced neutrophilrich airway inflammation in OVA-specific TCR-expressing C57BL/6-OTII mice. We then used a combination of pharmacologic and genetic approaches to investigate the potential roles of individual mediators, cytokines, and chemoattractants in the development of the neutrophil-rich airway inflammation induced by Ag challenge in this model. Finally, we used a genetic approach to investigate the roles of FcR␥, mast cells, and mast cell-derived TNF in this model of Ag-and Th17 cell-dependent, neutrophil-rich airway inflammation. The online version of this article contains a data supplement...

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Neutrophils in asthma pathophysiology

Cited by 70 publications

References 72 publications

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

Mast cell–derived TNF can promote Th17 cell–dependent neutrophil recruitment in ovalbumin-challenged OTII mice

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