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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2010;3(3):233-244
Review Article
Role of the CX3CL1-CX3CR1 axis in chronic inflammatory lung diseases
Jianliang Zhang, Jawaharlal M. Patel
Department of Medicine, University of Florida College of Medicine; and Research Service, Malcom Randall Department of Veterans
Affairs Medical Center, Gainesville, FL 32608-1197, USA
Received July 7, 2010; accepted July 31, 2010; available online August 10, 2010
Abstract: Persistent inflammation is often present in patients with lung diseases such as chronic obstructive pulmonary diseases
(COPD) and pulmonary hypertension. Circulatory leukocyte migration through the lung vascular endothelium contributes to the
structural destruction and remodeling seen in these chronic lung diseases. An inflammatory chemokine CX3CL1/fractalkine is
associated with inflammatory lung diseases. Membrane-anchored CX3CL1 serves as an adhesion molecule to capture subsets of
mononuclear leukocytes that express the sole receptor, CX3CR1. The extracellular chemokine domain of CX3CL1 can be
cleaved/shed by a disintegrin and metalloproteinase domain (ADAM) from stimulus-exposed cells. Soluble CX3CL1 chemoattracts and
activates CX3CR1+ leukocytes such as CD8+, CD4+, and γδ T lymphocytes, natural killer cells, dendritic cells, and
monocytes/macrophages. CX3CR1+ leukocyte attachment to and migration through the lung vascular endothelium lead to
mononuclear cell accumulation in the lung vessel walls and parenchyma. Infiltrated CX3CR1+ immune cells can release mediators to
induce injury, stimulate proliferation, and/or chemoattract inflammatory cells. This contributes to structural destruction and remodeling
in the development of inflammatory lung diseases. Limited clinical success in treating chronic pulmonary diseases-associated lung
functional decline indicates the urgency and significance of understanding upstream signaling that triggers inflammation. This article
reviews the advances in the CX3CL1-CX3CR1 axis-mediated modulation of mononuclear leukocyte adhesion and migration in
inflammatory lung diseases such as COPD and pulmonary hypertension. Better understanding of the constant flow of circulating
leukocytes into the lung vessel wall and parenchyma will help set a stage for the development of novel therapeutic approaches to treat
or even cure chronic lung diseases including COPD and pulmonary hypertension. (IJCEM1007001).
Keywords: Chemokine, fractalkine, inflammation, pulmonary, COPD, endothelium, vasculature
Full Text PDF
Address all correspondence to:
Jianliang Zhang, PhD
Pulmonary Division, MSB Rm M452
Department of Medicine
University of Florida College of Medicine
1600 S. W. Archer Road, Gainesville
FL 32610-0225, USA.
Tel: 353-376-1611, Ext. 6265, Fax: 352-374-6170
E-mail: Zhangjl@medicine.ufl.edu
Review Article
Role of the CX3CL1-CX3CR1 axis in chronic inflammatory lung diseases
Jianliang Zhang, Jawaharlal M. Patel
Department of Medicine, University of Florida College of Medicine; and Research Service, Malcom Randall Department of Veterans
Affairs Medical Center, Gainesville, FL 32608-1197, USA
Received July 7, 2010; accepted July 31, 2010; available online August 10, 2010
Abstract: Persistent inflammation is often present in patients with lung diseases such as chronic obstructive pulmonary diseases
(COPD) and pulmonary hypertension. Circulatory leukocyte migration through the lung vascular endothelium contributes to the
structural destruction and remodeling seen in these chronic lung diseases. An inflammatory chemokine CX3CL1/fractalkine is
associated with inflammatory lung diseases. Membrane-anchored CX3CL1 serves as an adhesion molecule to capture subsets of
mononuclear leukocytes that express the sole receptor, CX3CR1. The extracellular chemokine domain of CX3CL1 can be
cleaved/shed by a disintegrin and metalloproteinase domain (ADAM) from stimulus-exposed cells. Soluble CX3CL1 chemoattracts and
activates CX3CR1+ leukocytes such as CD8+, CD4+, and γδ T lymphocytes, natural killer cells, dendritic cells, and
monocytes/macrophages. CX3CR1+ leukocyte attachment to and migration through the lung vascular endothelium lead to
mononuclear cell accumulation in the lung vessel walls and parenchyma. Infiltrated CX3CR1+ immune cells can release mediators to
induce injury, stimulate proliferation, and/or chemoattract inflammatory cells. This contributes to structural destruction and remodeling
in the development of inflammatory lung diseases. Limited clinical success in treating chronic pulmonary diseases-associated lung
functional decline indicates the urgency and significance of understanding upstream signaling that triggers inflammation. This article
reviews the advances in the CX3CL1-CX3CR1 axis-mediated modulation of mononuclear leukocyte adhesion and migration in
inflammatory lung diseases such as COPD and pulmonary hypertension. Better understanding of the constant flow of circulating
leukocytes into the lung vessel wall and parenchyma will help set a stage for the development of novel therapeutic approaches to treat
or even cure chronic lung diseases including COPD and pulmonary hypertension. (IJCEM1007001).
Keywords: Chemokine, fractalkine, inflammation, pulmonary, COPD, endothelium, vasculature
Full Text PDF
Address all correspondence to:
Jianliang Zhang, PhD
Pulmonary Division, MSB Rm M452
Department of Medicine
University of Florida College of Medicine
1600 S. W. Archer Road, Gainesville
FL 32610-0225, USA.
Tel: 353-376-1611, Ext. 6265, Fax: 352-374-6170
E-mail: Zhangjl@medicine.ufl.edu
