T Lymphocytes and Activated Eosinophils in Airway Mucosa in Fatal Asthma and Cystic Fibrosis

Azzawi, May; Johnston, Patricia; Majumdar, S.; Kay, A. B.; Jeffery, Peter K.

doi:10.1164/ajrccm/145.6.1477

Cited by 165 publications

(99 citation statements)

References 9 publications

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“…In cases of fatal asthma, the numbers of eosinophils were more closely related to the number of lymphocytes than in the nonfatal asthma and control cases. Numerous studies [3,12,15,16,19,20,24,[32][33][34] have shown increased numbers both of lymphocytes and eosinophils in asthmatic airways, although not over the range of asthma severity and airway sizes sampled in this study. It has been suggested that cell/ endothelial adhesion mechanisms and chemoattractant cytokines [35][36][37][38] may provide a common pathway of extravasation for lymphocytes and eosinophils at sites of inflammation.…”

Section: Discussionmentioning

confidence: 52%

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

Carroll

Cooke²,

James³

1997

Eur Respir J

246

164

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Airway inflammation in asthma consists of variably increased numbers of mononuclear and polymorphonuclear cells, and there is a growing body of evidence to suggest a primary role for lymphocytes and eosinophils in the pathogenesis of asthma. The aim of this study was to examine the distribution of lymphocytes and eosinophils in the bronchial tree of cases of mild and severe asthma.In cases of fatal asthma (n=10), nonfatal asthma (sudden nonrespiratory death with a history of asthma n=10), and control cases (sudden death with no history of respiratory illness, n=10), lymphocytes and eosinophils were counted in transverse sections of large and small airways stained with haematoxylin and eosin.Cases of fatal asthma had longstanding severe asthma and nonfatal cases generally had mild asthma. Lymphocytes were increased in all airway size groups both in fatal and nonfatal cases of asthma compared to control cases (p<0.001). Eosinophils were increased (p<0.001) in all airway size groups in the cases of fatal asthma compared to the nonfatal asthma and control groups, which were similar. These differences between case groups were of similar magnitude, when only a random single airway section from each case in each size group was examined. The numbers of lymphocytes correlated with the number of eosinophils in the fatal asthma group (r=0.60; p<0.0001), and to a lesser extent in the nonfatal (r=0.34; p=0.001) and control groups (r=0.32; p=0.001).These findings suggest that increased numbers of lymphocytes are uniformly distributed in the large and small airways in cases of asthma, independently of asthma severity, and that eosinophil recruitment may be related to asthma severity. Hence, biopsy specimens of the proximal airways are likely to be representative of the cellular infiltrate in large and small airways in mild and severe asthma.

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Section: Discussionmentioning

confidence: 52%

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

Carroll

Cooke²,

James³

1997

Eur Respir J

246

164

View full text Add to dashboard Cite

show abstract

“…Presence of CD80, major histocompatibility class II, and the Th2-associated receptor CD294 on the surface of CF airway neutrophils suggests that these cells are undergoing a significant switch toward cooperative functions with T cells, as described in other chronic inflammatory conditions (20,22). T cells migrate to the CF airway mucosa (38) and could play a nonnegligible role in neutrophil immunomodulation (2). Further studies are needed to determine whether de novo receptor expression by neutrophils plays a role in mitigating or accelerating CF airway inflammation.…”

Section: Discussionmentioning

confidence: 97%

Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways

Tirouvanziam

Gernez²,

Conrad³

et al. 2008

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

127

169

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Blood neutrophils recruited to cystic fibrosis (CF) airways are believed to be rapidly killed by resident bacteria and to passively release elastase and other toxic by-products that promote disease progression. By single-cell analysis, we demonstrate that profound functional and signaling changes readily occur within viable neutrophils recruited to CF airways, compared with their blood counterparts. Airway neutrophils have undergone conventional activation, as shown by decreased intracellular glutathione, increased lipid raft assembly, surface mobilization of CD11b؉ and CD66b؉ granules, and increased levels of the cytoskeleton-associated phospho-Syk kinase. Unexpectedly, they also mobilize to the surface CD63؉ elastase-rich granules, usually confined intracellularly, and lose surface expression of CD16 and CD14, both key receptors in phagocytosis. Furthermore, they express CD80, major histocompatibility complex type II, and the prostaglandin D2 receptor CD294, all normally associated with other lineages, which reflects functional reprogramming. This notion is reinforced by their decreased total phosphotyrosine levels, mirroring a postactivated stage, and increased levels of the phospho-S6 ribosomal protein, a key anabolic switch. Thus, we identified a subset of neutrophils within CF airways with a viable but dysfunctional phenotype. This subset provides a possible therapeutic target and indicates a need to revisit current paradigms of CF airway disease.cystic fibrosis transmembrane conductance regulator ͉ flow cytometry ͉ inflammation ͉ lung disease ͉ phosphoepitope

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“…In acute allergic airway inflammation, eosinophils and macrophages constitute >80% of total recovered leukocytes 3,5,14 . Although allergic inflammation may be harmful to any organ, the host is particularly susceptible to lung involvement due to the potentially lethal effects of the inflammatory cells on gas exchange 39 . We showed that 100% mortality occurred in MMP2 −/− mice compared to 20% in wild-type mice (P<0.008).…”

Section: Discussionmentioning

confidence: 99%

Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency

et al. 2002

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Clearance of recruited immune cells is necessary to resolve inflammatory reactions. We show here that matrix metalloproteinase 2 (MMP2), as part of an interleukin 13 (IL-13)-dependent regulatory loop, dampens inflammation by promoting the egress of inflammatory cells into the airway lumen. MMP2 −/− mice showed a robust asthma phenotype and increased susceptibility to asphyxiation induced by allergens. However, whereas the lack of MMP2 reduced the influx of cells into bronchoalveolar lavage (BAL), numerous inflammatory cells accumulated in the lung parenchyma. BAL of MMP2 −/− mice lacked normal chemotactic activity, whereas lung inflammatory cells from the same mice showed appropriate chemotactic responses. Thus, MMP2 establishes the chemotactic gradient required for egression of lung inflammatory cells and prevention of lethal asphyxiation.

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T Lymphocytes and Activated Eosinophils in Airway Mucosa in Fatal Asthma and Cystic Fibrosis

Cited by 165 publications

References 9 publications

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways

Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency

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