Small airway obstruction in severe pulmonary arterial hypertension correlates with increased airway CD8+ T-cells and fractalkine expression

Ars, Catherine; Thurion, Pascal; Delos, Monique; Sibille, Yves; Pilette, Charles

doi:10.1183/09031936.00140109

Cited by 12 publications

(8 citation statements)

References 13 publications

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“…The membrane form mediates cell-cell adhesion by binding CX 3 CR1 on adjacent cells whereas both the soluble and membrane forms of CX 3 CL1 may mediate chemotactic and angiogenic responses by activating CX 3 CR1 in relevant cell types [12, 33, 34]. Alterations in CX 3 CL1/CX 3 CR1 have been found in a number of conditions affecting liver and lung[14, 15, 35, 36], and in several of these conditions CX 3 CL1/CX 3 CR1 signaling contributes to monocyte accumulation and angiogenesis [7]. A variety of factors relevant to liver disease may influence CX 3 CL1 expression (interferon-gamma, TNF-α, IL-1β, shear stress and endothelin-1) [37] and CX 3 CR1 expression [38].…”

Section: Discussionmentioning

confidence: 99%

The role of CX3CL1/CX3CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome

Zhang

Luo

et al. 2012

Journal of Hepatology

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Background & Aims Hepatopulmonary syndrome (HPS), classically attributed to intrapulmonary vascular dilatation, occurs in 15-30% of cirrhotics and causes hypoxemia and increased mortality. In experimental HPS after common bile duct ligation (CBDL), monocytes adhere in the lung vasculature and produce vascular endothelial growth factor (VEGF)-A and angiogenesis ensues and contributes to abnormal gas exchange. However, the mechanisms for these events are unknown. The chemokine fractalkine (CX3CL1) can directly mediate monocyte adhesion and activate VEGF-A and angiogenesis via its receptor CX3CR1 on monocytes and endothelium during inflammatory angiogenesis. We explored whether pulmonary CX3CL1/CX3CR1 alterations occur after CBDL and influence pulmonary angiogenesis and HPS. Methods Pulmonary CX3CL1/CX3CR1 expression and localization, CX3CL1 signaling pathway activation, monocyte accumulation, and the development of angiogenesis and HPS were assessed in 2 and 4wk CBDL animals. The effects of a neutralizing antibody to CX3CR1 (anti-CX3CR1 Ab) on HPS after CBDL were evaluated. Results Circulating CX3CL1 levels and lung expression of CX3CL1 and CX3CR1 in intravascular monocytes and microvascular endothelium increased in 2 and 4wk CBDL animals as HPS developed. These events were accompanied by pulmonary angiogenesis, monocyte accumulation, activation of CX3CL1 mediated signaling pathways (Akt, ERK) and increased VEGF-A expression and signaling. Anti-CX3CR1 Ab treatment reduced monocyte accumulation, decreased lung angiogenesis and improved HPS. These events were accompanied by inhibition of CX3CL1 signaling pathways and a reduction in VEGF-A expression and signaling. Conclusions Circulating CX3CL1 levels and pulmonary CX3CL1/CX3CR1 expression and signaling increase after CBDL and contribute to pulmonary intravascular monocyte accumulation, angiogenesis and the development of experimental HPS.

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Section: Discussionmentioning

confidence: 99%

The role of CX3CL1/CX3CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome

Zhang

Luo

et al. 2012

Journal of Hepatology

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“…CD8 + T cells are activated by cDC1s ( 19 , 27 ). In patients with IPAH, circulating CD8 + T cells portion decreased compared with control subjects ( 46 ), but increased in PAH lung tissues, especially in obstructed sites ( 46 , 47 ). Single-cell sequencing identified increased CD8 + T cells proportion in lung tissues of patients with IPAH ( 21 ), however, its role in PAH development needs more experimental exploration.…”

Section: Immune Cells Involved In Adaptive Immunitymentioning

confidence: 93%

Autoimmunity in Pulmonary Arterial Hypertension: Evidence for Local Immunoglobulin Production

Shu

Xing

Wang

2021

Front. Cardiovasc. Med.

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Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease. The notion that autoimmunity is associated with PAH is widely recognized by the observations that patients with connective tissue diseases or virus infections are more susceptible to PAH. However, growing evidence supports that the patients with idiopathic PAH (IPAH) with no autoimmune diseases also have auto-antibodies. Anti-inflammatory therapy shows less help in decreasing auto-antibodies, therefore, elucidating the process of immunoglobulin production is in great need. Maladaptive immune response in lung tissues is considered implicating in the local auto-antibodies production in patients with IPAH. In this review, we will discuss the specific cell types involved in the lung in situ immune response, the potential auto-antigens, and the contribution of local immunoglobulin production in PAH development, providing a theoretical basis for drug development and precise treatment in patients with PAH.

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“…Transmembrane CX3CL1 may transduce a cell survival signal [69,70], or promote adhesive interactions and retention of CX3CR1 + mononuclear phagocytes. The principal cell type producing transmembrane CX3CL1 remains to be identified in human lungs, but the bronchial epithelium [71], airway smooth muscle cells [72,73], and endothelial cells [71,74] have been previously implicated. Metalloproteinases (MMP) such as A Disintegrin And Metalloproteinase (ADAM)-17 or ADAM-10 cleave transmembrane CX3CL1 [75–77] and the soluble chemokine form of CX3CL1 may promote inflammatory cytokine release, tissue damage, and amplify the recruitment of other cell types such as neutrophils or T-lymphocytes.…”

Section: Figurementioning

confidence: 99%

Heterogeneity of Lung Mononuclear Phagocytes in Chronic Obstructive Pulmonary Disease

Lee

2012

J Innate Immun

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Chronic obstructive pulmonary disease (COPD) is a disease defined by an aberrant inflammatory response to inhaled cigarette smoke and other noxious particles. The factors triggered in the lungs that drive inflammation and lung tissue destruction are not fully understood, but mononuclear phagocytes play a central role by releasing mediators that promote both inflammation and tissue-destructive emphysema. Although conflicting studies on alveolar macrophages exist regarding chronic cigarette smoke exposure and its effects on macrophage polarization patterns, we have recently identified a cell type in mice defined by CX3CR1 expression. The population of this cell type expands in the lungs and elaborates M1 signature cytokines in response to cigarette smoke exposure in vivo. In addition, the absence of functional CX3CR1 provides protection from tissue-destructive emphysema in a murine model of chronic cigarette smoke exposure. The heterogeneity and plasticity of discrete macrophage subsets, in terms of immunophenotype and function, may explain the seemingly disparate findings showing a suppressed inflammatory profile on the one hand and a heightened inflammatory response on the other. This review examines the evidence that discrete mononuclear phagocyte subsets develop in response to cigarette smoke exposure, and that the spatial cues provided by the lung tissue microenvironment in which the mononuclear phagocytes reside may influence the distribution and function of these subsets.

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Small airway obstruction in severe pulmonary arterial hypertension correlates with increased airway CD8+ T-cells and fractalkine expression

Cited by 12 publications

References 13 publications

The role of CX3CL1/CX3CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome

The role of CX3CL1/CX3CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome

Autoimmunity in Pulmonary Arterial Hypertension: Evidence for Local Immunoglobulin Production

Heterogeneity of Lung Mononuclear Phagocytes in Chronic Obstructive Pulmonary Disease

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