Accumulation of CXCR3-Expressing Eosinophils and Increased Concentration of Its Ligands (IP10 and Mig) in Bronchoalveolar Lavage Fluid of Patients with Chronic Eosinophilic Pneumonia

Katoh, Shigeki; Fukushima, Kiyoyasu; Matsumoto, Nobuhiro; Ehara, Naomi; Matsumoto, Kiyoshi; Yamauchi, Akira; Hirashima, Mitsuomi

doi:10.1159/000086335

Cited by 24 publications

(26 citation statements)

References 53 publications

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“…In both cases correlations were found to the absolute number of lymphocytes in the BALF. Similarly, Katoh et al [17] found elevated BALF levels of IP10 and MIG in patients with chronic eosinophilic pneumonitis. Furthermore, other investigators [15], [18] have found associations between IP10 and interstitial lung diseases.…”

Section: Discussionmentioning

confidence: 82%

Effect of Different Interferonα2 Preparations on IP10 and ET-1 Release from Human Lung Cells

et al. 2012

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BackgroundAlfa-interferons (IFNα2a, IFNα2b, 40KDa-PEGIFNα2a and 12KDa-PEGIFNα2b) are effective treatments for chronic hepatitis C infection. However, their usage has been associated with a variety of adverse events, including interstitial pneumonitis and pulmonary arterial hypertension. Although rare, these adverse events can be severe and potentially life-threatening, emphasizing the need for simple biomarkers of IFN-induced lung toxicity.MethodsHuman lung microvascular endothelial cells (HLMVEC), human pulmonary artery smooth muscle (HPASM) cells and A549 cells were grown under standard conditions and plated into 96- or 6-well plates. Cells were stimulated with various concentrations of different IFNs in hydrocortisone-free medium. After 24 and 48 hours, IP10 and ET-1 were measured by ELISA in conditioned medium. In a second set of experiments, cells were pre-treated with tumour necrosis factor-α (TNF-α) (10 ng/mL).ResultsIFNα2a, IFNα2b, 40KDa-PEGIFNα2a and 12KDa-PEGIFNα2b, but not IFNλ, induced IP10 (CXCL10) release and increased IP10 gene induction in HLMVEC. In addition, all four IFNα preparations induced IP10 release from HPASM cells and A549 cells pre-treated with TNFα. In each of these cell types, 40KDa-PEGIFNα2a was significantly less active than the native forms of IFNα2a, IFNα2b or 12KDa-PEGIFNα2b. Similarly, IFNα2a, IFNα2b and 12KDa-PEGIFNα2b, but not 40KDa-PEGIFNα2a, induced endothelin (ET)-1 release from HPASM cells.ConclusionsConsistent with other interstitial pulmonary diseases, both IP10 and ET1 may serve as markers to monitor IFN-induced lung toxicity in patients. In addition, both markers may also serve to help characterize the risk associated with IFNα preparations to induce lung toxicity.

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Section: Discussionmentioning

confidence: 82%

Effect of Different Interferonα2 Preparations on IP10 and ET-1 Release from Human Lung Cells

et al. 2012

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“…Several chemokines are also present in BAL fluid samples, including CCL17 and CCL22, the chemokine ligands of the receptor CCR4, suggesting that T cell recruitment may be an important factor in the pathophysiology of CEP (74,114). In addition, CXCL9, CXCL10, CCL5 (RANTES), CCL11 (eotaxin-1), CCL2, and CCL4 have also been observed to be elevated in CEP (73,75,89,186). Other immune mediators, such as tryptase, prostaglandins, and soluble ADAM8, have been detected to be elevated in the BAL fluid of CEP patients as well (7,109,132).…”

Section: Cepmentioning

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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“…For example, Liu et al reported that eosinophils in the airway express more CXCR3 and less CCR3 than those in peripheral blood [36]. Katoh et al found higher ratios of CXCR3-expressing eosinophils in BALF than in peripheral blood [37]. Nagase et al reported that less CCR3 is expressed by eosinophils in BALF than in peripheral blood [38].…”

Section: Discussionmentioning

confidence: 99%

IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β2integrin and CXCR3

et al. 2011

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BackgroundEosinophils play an important role in the pathogenesis of bronchial asthma and its exacerbation. Recent reports suggest the involvement of IFN-γ-inducible protein of 10 kDa (IP-10) in virus-induced asthma exacerbation. The objective of this study was to examine whether CXCR3 ligands including IP-10 modify the effector functions of eosinophils.MethodsEosinophils isolated from the blood of healthy donors were stimulated with CXCR3 ligands and their adhesion to rh-ICAM-1 was then measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O2-) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated to determine whether CXCR3 ligands induced eosinophil degranulation. Cytokine and chemokine production by eosinophils was examined using a Bio-plex assay.ResultsEosinophil adhesion to ICAM-1 was significantly enhanced by IP-10, which also significantly induced eosinophil O2- generation in the presence of ICAM-1. Both the enhanced adhesion and O2- generation were inhibited by an anti-β2 integrin mAb or an anti-CXCR3 mAb. Other CXCR3 ligands, such as monokine induced by IFN-γ (Mig) and IFN-inducible T cell α chemoattractant (I-TAC), also induced eosinophil adhesion and O2- generation in the presence of ICAM-1. IP-10, but not Mig or I-TAC, increased the release of EDN. IP-10 increased the production of a number of cytokines and chemokines by eosinophils.ConclusionsThese findings suggest that CXCR3 ligands such as IP-10 can directly upregulate the effector functions of eosinophils. These effects might be involved in the activation and infiltration of eosinophils in the airway of asthma, especially in virus-induced asthma exacerbation.

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Accumulation of CXCR3-Expressing Eosinophils and Increased Concentration of Its Ligands (IP10 and Mig) in Bronchoalveolar Lavage Fluid of Patients with Chronic Eosinophilic Pneumonia

Cited by 24 publications

References 53 publications

Effect of Different Interferonα2 Preparations on IP10 and ET-1 Release from Human Lung Cells

Effect of Different Interferonα2 Preparations on IP10 and ET-1 Release from Human Lung Cells

Eosinophilic Pneumonias

IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β2integrin and CXCR3

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