Epithelial Injury by Human Eosinophils

Venge, Per; Dahl, Ronald; Fredens, Kjeld; Peterson, Christer

doi:10.1164/ajrccm/138.6_pt_2.s54

Cited by 135 publications

(65 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of eosinophil-derived reactive oxygen metabolites in producing damage to the airway epithelium has been recognized as a major factor in the pathophysiology of asthma (8)(9)(10)(11)14). Consequently, drugs that modify eosinophil production, trafficking, or activation should be of use in the treatment of this disease.…”

Section: Discussionmentioning

confidence: 99%

“…Activated eosinophils release both proinflammatory and cytotoxic substances (3,8,9). In particular, these cells release cationic proteins (e.g., major basic protein, eosinophil cationic protein) and reactive oxygen metabolites (e.g., superoxide, singlet oxygen) (8)(9)(10). Hypothetically, these substances act in concert to destroy epithelial cell membranes.…”

Section: Introductionmentioning

confidence: 99%

“…Eosinophils are recruited into asthmatic airways and activated by a variety of lipid mediators (e.g., leukotriene B4, platelet activating factor) and cytokines (e.g., tumor necrosis factor-a, interleukin-5) (3,8). Activated eosinophils release both proinflammatory and cytotoxic substances (3,8,9). In particular, these cells release cationic proteins (e.g., major basic protein, eosinophil cationic protein) and reactive oxygen metabolites (e.g., superoxide, singlet oxygen) (8-10).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Phosphodiesterase IV Inhibitors as Therapy for Eosinophil-Induced Lung Injury in Asthma

Torphy¹,

Barnette²,

Hay³

et al. 1994

Environmental Health Perspectives

View full text Add to dashboard Cite

Asthma is a complex, multifactorial disease that is underpinned by airway inflammation. A variety of cytotoxic substances are released into the airway from infiltrating inflammatory cells, especially the eosinophil. These cytotoxic substances, including reactive oxygen metabolites, produce damage to the airway epithelium, a histologic feature of chronic asthma. Damage to the airway epithelium, in turn, is thought to be a major factor responsible for the development of airway hyperreactivity, a hallmark of asthma. One notable molecular target for novel antiasthmatic drugs is the cyclic AMP-specific phosphodiesterase (PDE) or PDE IV. This isozyme is the predominant form of cyclic nucleotide PDE activity in inflammatory cells. Thus, in view of the putative role of cyclic AMP as an inhibitory second messenger in these cells, PDE IV inhibitors have been shown to suppress inflammatory cell activity. The purpose of the present experiments was to examine the effect of the PDE IV inhibitor, R-rolipram, on three key functions of the guinea pig eosinophil: a) superoxide anion (°O) production, b) adhesion to human umbilical vein endothelial cells (HUVECs), and c) infiltration into the airway. R-rolipram-elevated eosinophil cyclic AMP content (EC50= 1.7 pM) and inhibited fMLP-induced°2 production in a concentration-dependent manner (IC50=0.3 pM). In contrast, neither siguazodan, a PDE IlIl inhibitor, nor zaprinast, a PDE V inhibitor, had an appreciable effect. R-rolipram (30 pM) also reduced by 25 to 40% the adhesion of eosinophils to HUVECs stimulated with phorbol myristate acetate or tumor necrosis factor-a, particularly under conditions in which both cell types were simultaneously exposed to the PDE IV inhibitor. Again, siguazodan and zaprinast had little or no effect. Finally, pretreatment of conscious guinea pigs with R-rolipram (1-10 mg/kg, intragastric) produced a dose-dependent inhibition of antigen-induced eosinophil infiltration into the airway. Thus, by virtue of their ability to modify eosinophil function at several levels, PDE IV inhibitors may reduce epithelial cell damage associated with asthma. - 270-5381. that the loss of the airway epithelium leads to airway hyperreactivity by exposing subepithelial sensory nerve endings to the external environment (6,7). Consequently, noxious environmental stimuli more easily activate these nerve endings to cause antidromic release of bronchoconstricting neuropeptides (e.g., substance P) from Cfibers via an axon reflex (6,7).The inflammatory cell primarily responsible for damaging the airway epithelium is the eosinophil (Figure 1). Eosinophils are recruited into asthmatic airways and activated by a variety of lipid mediators (e.g., leukotriene B4, platelet activating factor) and cytokines (e.g., tumor necrosis factor-a, interleukin-5) (3,8). Activated eosinophils release both proinflammatory and cytotoxic substances (3,8,9). In particular, these cells release cationic proteins (e.g., major basic protein, eosinophil cationic protein) and reactive oxygen metabolites (e.g...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Phosphodiesterase IV Inhibitors as Therapy for Eosinophil-Induced Lung Injury in Asthma

Torphy¹,

Barnette²,

Hay³

et al. 1994

Environmental Health Perspectives

View full text Add to dashboard Cite

show abstract

“…[2][3][4][5][6][7][8][9] The cellular inflammatory response of the bronchial mucosa is characterized by infiltration of eosinophils, [4][5][6][7]9 and activated eosinophils are able to release many cytotoxic proteins, including eosinophil cationic protein (ECP), which plays a central role in bronchial epithelial damage. [10][11] Various outcomes are being used to evaluate the severity of disease and to assess response to therapy in chronic bronchial asthma. Traditionally, measurement of airway function, especially spirometry, has been the primary means of evaluating and assessing patients with asthma.…”

mentioning

confidence: 99%

Sputum analysis, bronchial hyperresponsiveness, and airway function in asthma: Results of a factor analysis

Rosi

Ronchi

Grazzini

et al. 1999

Journal of Allergy and Clinical Immunology

148

111

View full text Add to dashboard Cite

Background: Recent studies have shown weak associations among FEV 1 , bronchial hyperresponsiveness (BHR), sputum eosinophils, and sputum eosinophil cationic protein (ECP), suggesting that they are nonoverlapping quantities. The statistical method of factor analysis enables reduction of many parameters that characterize the disease to a few independent factors, with each factor grouping associated parameters. Objective: The purpose of this study was to demonstrate, by using factor analysis, that reversible airway obstruction, BHR, and eosinophilic inflammation of the bronchial tree, as assessed by cytologic and biochemical analysis of sputum, may be considered separate dimensions that characterize chronic bronchial asthma. Methods: Ninety-nine clinically stable patients with a previous diagnosis of asthma underwent spirometry, sputum induction, and histamine inhalation tests. Results: Most patients were nonobstructed (FEV 1 , 91% ± 20%); a low level of bronchial reversibility (FEV 1 increase after β 2 -agonist, 7.8% ± 9.2%) and BHR (histamine PC 20 FEV 1 geometric mean, 0.98 mg/mL) were found. Sputum eosinophil differential count (12.4% ± 17.7%) and sputum ECP (1305 ± 3072 µg/mL) were in the normal range of our laboratory in 38 and 22 patients, respectively. Factor analysis selected 3 different factors, explaining 74.8% of variability. Measurements of airway function and age loaded on factor I, PC 20 FEV 1 and β 2 -response loaded on factor II, and sputum ECP and eosinophils loaded on factor III. Additional post hoc factor analyses provided similar results when the sample was divided into 2 subgroups by randomization, presence of airway obstruction, degree of BHR, percentage of sputum eosinophils, or concentration of sputum ECP. Conclusions: We conclude that airway function, baseline BHR, and airway inflammation may be considered separate dimensions in the description of chronic asthma. Such evidence supports the utility of routine measurement of all these dimensions. (J Allergy Clin Immunol 1999;103:232-7.)

show abstract

“…On activation, eosinophils release cationic granule proteins that exert cytotoxic effects on epithelial cells in vivo. 3 Daneshpouy et al 4 performed systematic duodenal biopsies immediately after gastric symptoms occurred and found that eosinophils were present only when there were histologic signs of GVHD; eosinophil presence correlated with GVHD severity, and they concluded that tissue eosinophil concentrations are a marker of acute inflammatory reaction during GVHD flare-ups. There are similar reports by Basara et al 5 in BM, based on a systematic prospective study of BM smears and biopsies.…”

mentioning

confidence: 99%

Eosinophilic cystitis following cord blood transplantation: a form of acute GVHD. A variant of hemorrhagic cystitis after hematopoietic SCT or drug-induced?

Tasaka

Matsuhashi

Ohnìshì

et al. 2008

Bone Marrow Transplant

View full text Add to dashboard Cite

Epithelial Injury by Human Eosinophils

Cited by 135 publications

References 13 publications

Phosphodiesterase IV Inhibitors as Therapy for Eosinophil-Induced Lung Injury in Asthma

Phosphodiesterase IV Inhibitors as Therapy for Eosinophil-Induced Lung Injury in Asthma

Sputum analysis, bronchial hyperresponsiveness, and airway function in asthma: Results of a factor analysis

Eosinophilic cystitis following cord blood transplantation: a form of acute GVHD. A variant of hemorrhagic cystitis after hematopoietic SCT or drug-induced?

Contact Info

Product

Resources

About