The role of CXC chemokines in pulmonary fibrosis

Strieter, Robert M.; Gomperts, Brigitte N.; Keane, Michael P.

doi:10.1172/jci30562

Cited by 241 publications

(223 citation statements)

References 106 publications

(152 reference statements)

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“…5 To dissect the mechanism of fibrocyte trafficking in response to liver injury, a CCR1 (or CCR2) receptor knockout mouse was crossed with a Col-Luc mouse and used for BM transplantation into lethally irradiated wild-type mice ( Figure 3D) 18 and undergo several stages of maturation. 19 Meanwhile, the BM counterpart of tissue fibrocytes has not been identified.…”

Section: Ccr2 and Ccr1 Regulate Fibrocyte Migration In Response To CCmentioning

confidence: 99%

“…4 Fibrocytes contribute to fibrogenesis of skin, lungs, kidneys, and liver. 5 It has been demonstrated that CD45 ϩ and collagen ␣1(I) ϩ fibrocytes migrate to the injured liver in response to cholestasis 4 and comprise approximately 3% to 5% of the cells producing collagen type I. Despite low numbers, inhibition of fibrocyte recruitment via administration of human serum amyloid protein, 6 a natural inhibitor of fibrocyte migration and differentiation, effectively attenuated fibrosis in lungs, 7 kidneys, 8 and liver (our unpublished observation), emphasizing an important role for fibrocytes in fibrogenesis of parenchymal organs.…”

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confidence: 99%

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Migration of Fibrocytes in Fibrogenic Liver Injury

Scholten

Reichart

Paik

et al. 2011

The American Journal of Pathology

100

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CD45 ؉ and collagen I-positive (Col ؉ ) fibrocytes are implicated in fibrogenesis in skin, lungs, and kidneys. Fibrocyte migration in response to liver injury was investigated using bone marrow (BM) from chimeric mice expressing luciferase (Col-Luc¡wt) or green fluorescent protein (Col-GFP¡wt) under control of the ␣1(I) collagen promoter and enhancer, respectively. Monitored by luciferase expression, recruitment of fibrocytes was detected in CCl 4 -damaged liver and in spleen. Migration of CD45 ؉ Col ؉ fibrocytes was regulated by chemokine receptors CCR2 and CCR1, as demonstrated, respectively, by 50% and 25% inhibition of fibrocyte migration in Col-Luc CCR2؊/؊ ¡wt and Col-Luc CCR1؊/؊ ¡wt mice. In addition to CCR2 and CCR1, egress of BM CD45 ؉ Col ؉ cells was regulated by transforming growth factor-␤1 (TGF-␤1) and liposaccharide in vitro and in vivo, which suggests that release of TGF-␤1 and increased intestinal permeability have important roles in fibrocyte trafficking. In the injured liver, fibrocytes gave rise to (myo)fibroblasts. In addition, a BM population of CD45 ؉ Col ؉ cells capable of differentiation into fibrocytes in culture was identified. Egress of CD45 ؉ Col ؉ cells from BM was detected in the absence of injury or stress in aged mice but not in young mice. Development of liver fibrosis was also increased in aged mice and correlated with high numbers of liver fibrocytes. In conclusion, in response to liver injury, fibrocytes migrate from BM to the liver. Their migration is regulated by CCR2 and CCR1 but is compromised with age.

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Section: Ccr2 and Ccr1 Regulate Fibrocyte Migration In Response To CCmentioning

confidence: 99%

mentioning

confidence: 99%

Migration of Fibrocytes in Fibrogenic Liver Injury

Scholten

Reichart

Paik

et al. 2011

The American Journal of Pathology

100

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“…8,9,[12][13][14] Part of such host immune responses involves the production of antiviral and inflammatory cytokines and chemokines from infected airway epithelial cells and leukocytes, including interferon (IFN)-␣/␤, TNF-␣, IFN-␥, keratinocytederived chemokine (KC), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1)␣/␤, MIP-3␣, interferon-␥ inducible protein 10 (IP-10), and regulated on activation normal T-cell expressed and secreted (RANTES). 9,[15][16][17] Cytotoxic CD8 T cells play an important role in influenza viral clearance by lysing virus-infected cells, and effective viral clearance from the lung is usually achieved within 7 to 10 days after primary infection. 8,12,13 A strong CD4 T-helper response is believed to contribute to the generation of robust hu-moral responses, important for neutralization of the virus.…”

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confidence: 99%

Negative Regulation of Lung Inflammation and Immunopathology by TNF-α during Acute Influenza Infection

Damjanovic

Divangahi

Kugathasan

et al. 2011

The American Journal of Pathology

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Lung immunopathology is the main cause of influenzamediated morbidity and death, and much of its molecular mechanisms remain unclear. Whereas tumor necrosis factor-␣ (TNF-␣) is traditionally considered a proinflammatory cytokine, its role in influenza immunopathology is unresolved. We have investigated this issue by using a model of acute H1N1 influenza infection established in wild-type and TNF-␣-deficient mice and evaluated lung viral clearance, inflammatory responses, and immunopathology. Whereas TNF-␣ was up-regulated in the lung after influenza infection, it was not required for normal influenza viral clearance. However, TNF-␣ deficiency led not only to a greater extent of illness but also to heightened lung immunopathology and tissue remodeling. The severe lung immunopathology was associated with increased inflammatory cell infiltration, anti-influenza adaptive immune responses, and expression of cytokines such as monocyte chemoattractant protein-1 (MCP-1) and fibrotic growth factor, TGF-␤1. Thus, in vivo neutralization of MCP-1 markedly attenuated lung immunopathology and blunted TGF-␤1 production following influenza infection in these hosts. On the other hand, in vivo transgenic expression of MCP-1 worsened lung immunopathology following influenza infection in wild-type hosts. Thus, TNF-␣ is dispensable for influenza clearance; however, different from the traditional belief, this cytokine is critically required for negatively regulating the extent of lung immunopathology during acute influenza infection.

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“…Angiogenesis is a complex process regulated by numerous proangiogenic and angiostatic forces (25). Our laboratory has begun to determine the proangiogenic growth factors that may contribute to neovascularization in animal models of left pulmonary artery obstruction (24).…”

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confidence: 99%

Inhibition of CXCR₂attenuates bronchial angiogenesis in the ischemic rat lung

Sukkar¹,

Jenkins²,

Sánchez³

et al. 2008

Journal of Applied Physiology

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. Inhibition of CXCR 2 attenuates bronchial angiogenesis in the ischemic rat lung. J Appl Physiol 104: 1470-1475, 2008. First published March 6, 2008 doi:10.1152/japplphysiol.00974.2007.-Under conditions of chronic pulmonary ischemia, the bronchial circulation undergoes massive proliferation. However, little is known regarding the mechanisms that promote neovascularization. An expanding body of literature implicates the glutamic acid-leucine-arginine (ELRϩ) CXC chemokines and their G protein-coupled receptor, CXCR 2, as key proangiogenic components in the lung. We used a rat model of chronic pulmonary ischemia induced by left pulmonary artery ligation (LPAL) to study bronchial angiogenesis. Using a methacrylate mixture, we cast the systemic vasculature of the rat lung at weekly intervals after LPAL. Twenty-one days after LPAL, numerous large, tortuous bronchial arteries were observed surrounding the left main bronchus that penetrated the left lung parenchyma. In stark contrast, the right lung was essentially devoid of vessels. We quantified bronchial neovascularization using 15-m radiolabeled microspheres to measure systemic blood flow to the left lung (n ϭ 12 rats). Results showed that by 21 days after LPAL, bronchial blood flow to the ischemic left lung had increased Ͼ10-fold compared with controls 2 days after LPAL (P Ͻ 0.01). Focusing on the predominant rat CXC chemokine that signals through CXCR 2, we measured increased levels of cytokine-induced neutrophil chemoattractant-3 protein expression in left lung homogenates early (4 and 24 h; n ϭ 10 rats) after LPAL relative to paired right lung controls (P Ͻ 0.01). Treatment with a neutralizing antibody to CXCR 2 resulted in a significant decrease in neovascularization 21 days after LPAL (n ϭ 9 rats; P Ͻ 0.01). Our results confirm the time course of bronchial angiogenesis in the rat and suggest the importance of CXC chemokines in promoting systemic neovascularization in the lung. bronchial artery; cytokine-induced neutrophil chemoattractant-3; microspheres THE BRONCHIAL CIRCULATION is the systemic vascular supply to the lung and provides nutrient blood flow to conducting airways down to the level of the terminal bronchioles as well as nerves, lymph nodes, visceral pleura, and walls of large pulmonary vessels. It normally provides less than 1% of cardiac output to the lung but has been shown to increase to as much as 30% of the original pulmonary blood flow after chronic unilateral pulmonary artery obstruction (13). This pathological feature of bronchial angiogenesis occurs during conditions of chronic inflammation such as cystic fibrosis (4), asthma (12), pulmonary fibrosis (27), lung cancer (16), and chronic thromboembolic disease (18). In animal models, pulmonary ischemia resulting from chronic pulmonary artery obstruction has been shown to cause proliferation of the systemic circulation to the lung in sheep (5), pigs (8), dogs (13), rats (28), and mice (14). However, little is known regarding the mechanisms that promote growth of bronchial arteries in chroni...

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The role of CXC chemokines in pulmonary fibrosis

Cited by 241 publications

References 106 publications

Migration of Fibrocytes in Fibrogenic Liver Injury

Migration of Fibrocytes in Fibrogenic Liver Injury

Negative Regulation of Lung Inflammation and Immunopathology by TNF-α during Acute Influenza Infection

Inhibition of CXCR₂attenuates bronchial angiogenesis in the ischemic rat lung

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The role of CXC chemokines in pulmonary fibrosis

Cited by 241 publications

References 106 publications

Migration of Fibrocytes in Fibrogenic Liver Injury

Migration of Fibrocytes in Fibrogenic Liver Injury

Negative Regulation of Lung Inflammation and Immunopathology by TNF-α during Acute Influenza Infection

Inhibition of CXCR2attenuates bronchial angiogenesis in the ischemic rat lung

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Inhibition of CXCR₂attenuates bronchial angiogenesis in the ischemic rat lung