Pulmonary arterial remodeling induced by a Th2 immune response

Daley, E.; Emson, Claire; Guignabert, Christophe; Malefyt, René de Waal; Louten, Jennifer; Kurup, Viswanath P.; Hogaboam, Cory M.; Taraseviciene‐Stewart, Laimute; Voelkel, Norbert F.; Rabinovitch, Marlene; Grünig, Ekkehard; Grünig, Gabriele

doi:10.1084/jem.20071008

Cited by 235 publications

(241 citation statements)

References 72 publications

(96 reference statements)

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“…However, interestingly, similar structural alterations were present among all vessels, regardless of size or location. The present findings of vascular remodeling of pulmonary arteries, preseptal veins and microvessels at 1d are in accordance with previous findings in this model [21, 22] and more chronic allergen administration models [4, 20]. However, the sustained features of vascular remodeling even after 1 month of resolution, represents a novel observation.…”

Section: Discussionsupporting

confidence: 82%

“…Although the present study did not investigate any physiological effects, a recent study by Daley and colleagues [4] showed that pulmonary vascular remodeling, induced by allergic airway inflammation, does not result in pulmonary hypertension but rather in a hyper-reactive response to e.g. hypoxia.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the most intriguing finding of this study was that acute inflammation could result in similar remodeling as chronic inflammation. Furthermore, it appears that the type of allergen and the method of sensitization/exposure are of less importance, as similar alterations are present in both models [20,21,22], as well as in other models of allergic airway inflammation [4]. …”

Section: Discussionmentioning

confidence: 99%

“…Recent data suggest that, similar to the airways, also the pulmonary circulation is affected and undergoes remodeling as a result of allergic airway inflammation [4,5,6,7,8]. However, this remodeling, which affects the large and mid-sized pulmonary vessels, is far less studied than the structural changes in asthmatic bronchi.…”

Section: Introductionmentioning

confidence: 99%

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Allergic Airway Inflammation Initiates Long-Term Vascular Remodeling of the Pulmonary Circulation

Rydell‐Törmänen¹,

Uller²,

Erjefält³

2009

Int Arch Allergy Immunol

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Background: Asthma and allergic airway inflammation are associated with persistent structural alterations in the bronchi, i.e. airway remodeling. Previous studies have shown that during allergic airway inflammation, similar structural alterations may also be evoked in the pulmonary circulation. However, it remained unknown whether remodeling of the pulmonary circulation is as persistent as airway remodeling. The aim of this study is to investigate the reversibility and resolution of vascular remodeling, induced by allergic airway inflammation. Methods: A validated mouse model of allergic airway inflammation, utilizing ovalbumin as allergen, was employed. Animals were sacrificed 1 day, 1 week or 1 month after the last allergen exposure, and different parameters of remodeling (smooth muscle mass, proliferation of smooth muscle cells and endothelial cells as well as number of myofibroblasts and procollagen-I-producing cells) were investigated and quantified histologically. Results: Allergen exposure resulted in allergic airway inflammation characterized by a transient leukocyte infiltration and in structural alterations in both airway and vascular compartments. The increase in vascular smooth muscle mass and endothelial proliferation persisted at 1 month after the last allergen exposure. The other parameters and cellular inflammatory response returned to baseline within 1 month after the last allergen challenge. Conclusions: Based on the findings in this study, we conclude that acute allergic airway inflammation, although being initiated from the airways, is able to evoke similar long-term structural alterations in pulmonary vessels as described for bronchi.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Allergic Airway Inflammation Initiates Long-Term Vascular Remodeling of the Pulmonary Circulation

Rydell‐Törmänen¹,

Uller²,

Erjefält³

2009

Int Arch Allergy Immunol

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“…These characteristics are mainly mediated by antigen-specific Th2 cells and their cytokines including interleukin (IL)-4, IL-5 and IL-13 [1]. Recently, Daley et al [2] demonstrated that repeated exposure of the airways of antigen-sensitized mice to antigens not only induces Th2 cell-mediated inflammation in the lung but also causes pulmonary arterial remodeling, suggesting that Th2 cell-mediated immune responses may cause pulmonary arterial remodeling at the site of allergic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-25 Induces Pulmonary Arterial Remodeling via Natural Killer T Cell-Dependent Mechanisms

Kawashima¹,

Hirose²,

Takahashi³

et al. 2013

Int Arch Allergy Immunol

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Background: Recent studies have shown that prolonged Th2-type immune inflammation in the lung induces pulmonary arterial remodeling, in part through the induction of resistin-like molecule α (RELMα) expression. However, the role of interleukin-25 (IL-25; which promotes this inflammation) in the development of the pulmonary arterial remodeling remains unknown. Methods: Ovalbumin (OVA)-sensitized C57BL/6 mice were challenged with OVA inhalation 3 times a week for 3 weeks. The effects of neutralizing anti-IL-25 antibody on OVA-induced pulmonary arterial remodeling and RELMα expression in the lung were examined. The pulmonary arterial remodeling and RELMα expression in the lung were examined in lung-specific IL-25 transgenic mice (CC10 IL-25 mice) and CC10 IL-25 mice in a natural killer T (NKT) cell-deficient background (CC10 IL-25 NKT^-/- mice). Results: Repeated OVA inhalation induced pulmonary arterial wall thickening and the expression of IL-25 and RELMα mRNA in the lung in OVA-sensitized mice. Injection of neutralizing anti-IL-25 antibody inhibited OVA-induced pulmonary arterial wall thickening and RELMα expression in the lung. CC10 IL-25 mice, but not CC10 IL-25 NKT^-/- mice, spontaneously developed pulmonary arterial wall thickening and RELMα expression in the lung at 6 months of age. Conclusions: Prolonged expression of IL-25 in the lung induces pulmonary arterial wall thickening by NKT cell-dependent mechanisms.

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Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension

Christmann¹,

Hayes²,

Pendergrass³

et al. 2011

Arthritis & Rheumatism

125

124

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Objective To explore the relationship between biomarkers of pulmonary arterial hypertension (PAH), interferon (IFN)–regulated gene expression, and the alternative activation pathway in systemic sclerosis (SSc). Methods Peripheral blood mononuclear cells (PBMCs) were purified from healthy controls, patients with idiopathic PAH, and SSc patients (classified as having diffuse cutaneous SSc, limited cutaneous SSc [lcSSc] without PAH, and lcSSc with PAH). IFN-regulated and “PAH biomarker” genes were compared after supervised hierarchical clustering. Messenger RNA levels of selected IFN-regulated genes (Siglec1 and MX1), biomarker genes (IL13RA1, CCR1, and JAK2), and the alternative activation marker gene (MRC1) were analyzed on PBMCs and on CD14− and CD14+ cell populations. Interleukin-13 (IL-13) and IL-4 concentrations were measured in plasma by immunoassay. CD14, MRC1, and IL13RA1 surface expression was analyzed by flow cytometry. Results Increased PBMC expression of both IFN-regulated and biomarker genes distinguished SSc patients from healthy controls. Expression of genes in the biomarker cluster, but not in the IFN-regulated cluster, distinguished lcSSc with PAH from lcSSc without PAH. The genes CCR1 (P < 0.001) and JAK2 (P < 0.001) were expressed more highly in lcSSc patients with PAH compared with controls and mainly by CD14+ cells. MRC1 expression was increased exclusively in lcSSc patients with PAH (P < 0.001) and correlated strongly with pulmonary artery pressure (r = 0.52, P = 0.03) and higher mortality (P = 0.02). MRC1 expression was higher in CD14+ cells and was greatly increased by stimulation with IL-13. IL-13 concentrations in plasma were most highly increased in lcSSc patients with PAH (P < 0.001). Conclusion IFN-regulated and biomarker genes represent distinct, although related, clusters in lcSSc patients with PAH. MRC1, a marker for the effect of IL-13 on alternative monocyte/macrophage activation, is associated with this severe complication and is related to mortality.

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Pulmonary arterial remodeling induced by a Th2 immune response

Cited by 235 publications

References 72 publications

Allergic Airway Inflammation Initiates Long-Term Vascular Remodeling of the Pulmonary Circulation

Allergic Airway Inflammation Initiates Long-Term Vascular Remodeling of the Pulmonary Circulation

Interleukin-25 Induces Pulmonary Arterial Remodeling via Natural Killer T Cell-Dependent Mechanisms

Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension

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