Local Blockade of Allergic Airway Hyperreactivity and Inflammation by the Poxvirus-Derived Pan-CC-Chemokine Inhibitor vCCI

Dabbagh, Karim; Xiao, Yun; Smith, Craig A.; Stepick-Biek, Pamela; Kim, Sung G.; Lamm, Wayne J. E.; Liggitt, Denny; Lewis, David B.

doi:10.4049/jimmunol.165.6.3418

Cited by 66 publications

(36 citation statements)

References 28 publications

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“…57 This molecule has been shown to ameliorate some aspects of inflammatory disease. 58 A fifth novel finding of the present study is that MCP-1 enhances migration and the ability of VSMCs from young aortas to invade a Matrigel-coated filter that mimics the extracellular matrix and that after MCP-1 treatment, these features of young VSMCs are indistinguishable from those of early-passage VSMCs from older rats.…”

Section: Discussionmentioning

confidence: 68%

Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function

Spinetti

Wang

Monticone

et al. 2004

ATVB

163

176

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Objective-With age, rat arterial walls thicken and vascular smooth muscle cells (VSMCs) exhibit enhanced migration and proliferation. Monocyte chemotactic protein-1 (MCP-1) affects these VSMC properties in vitro. Because arterial angiotensin II, which induces MCP-1 expression, increases with age, we hypothesized that aortic MCP-1 and its receptor CCR2 are also upregulated and affect VSMC properties. Methods and Results-Both MCP-1 and CCR2 mRNAs and proteins increased in old (30-month) versus young (8-month) F344ϫBN rat aortas in vivo. Cellular MCP-1 and CCR2 staining colocalized with that of ␣-smooth muscle actin in the thickened aortas of old rats and were expressed by early-passage VSMCs isolated from old aortas, which, relative to young VSMCs, exhibited increased invasion, and the age difference was abolished by vCCI, an inhibitor of CCR2 signaling. MCP-1 treatment of young VSMCs induced migration and increased their ability to invade a synthetic basement membrane. The MCP-1-dependent VSMC invasiveness was blocked by vCCI. After MCP-1 treatment, migration and invasion capacities of VSMCs from young aortas no longer differed from those of VSMCs isolated from older rats. Key Words: chemokines Ⅲ aging Ⅲ aorta Ⅲ vascular smooth muscle cells Ⅲ invasion A ging is the major risk factor for the development of atherosclerosis and hypertension, which have an important impact on Western society because they lead to myocardial infarction, stroke, and heart failure. 1-3 Arterial remodeling accompanies advancing age in all species, from rodents to nonhuman primates to humans, and the mechanisms involved in this remodeling likely confer on aging the status of the major risk factor for vascular diseases. 1,2 Specific facets of age-associated remodeling include luminal dilation, thickening of the intimal and medial layers with cellular and extracellular matrix reorganization, increased stiffness, and endothelial dysfunction. 4 -6 Studies from our laboratory and others have shown that diffuse intimal thickening with aging is characterized by accumulation of fibronectin, collagen, and vascular smooth muscle cells (VSMCs), with an increase in matrix metalloproteinase (MMP)-2 and angiotensin II (Ang II) expression. [7][8][9][10][11] In addition, the expression of aortic intracellular adhesion molecule and transforming growth factor-␤1 markedly increases with age, and these molecules localize to MMP-2-staining positive areas. 12 Arterial aging is also characterized by an increase in NAD(P)H oxidase activity and reactive oxygen species production and a reduction in nitric oxide (NO) bioavailability. [13][14][15][16] In addition, increased arterial levels of proinflammatory cytokines, such as tumor necrosis factor-␣ and interleukin-6, among others, accompany aging. [17][18][19][20] Structural and biochemical changes that occur within large arteries with aging are accompanied by a shift of the VSMC phenotype from the "contractile" to the "synthetic" state, characterized by an increased proliferative and migratory responsiveness to...

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Section: Discussionmentioning

confidence: 68%

Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function

Spinetti

Wang

Monticone

et al. 2004

ATVB

163

176

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“…These proteins tightly bind and inhibit the action of CC chemokines but have low or no affinity for chemokines of other subfamilies, making them potent and specific anti-inflammatory agents with demonstrated effectiveness in vivo (18,25). An extensive binding study with vaccinia vCCI using Ͼ80 chemokines from several organisms revealed 26 CC chemokines that bind with high affinity, including 13 human chemokines, such as MCP-1 (monocyte chemoattractant protein 1), MIP-1␣, MIP-1␤, and RANTES (26).…”

Section: Resultsmentioning

confidence: 99%

“…Although some CKBPs interact with a very broad spectrum of chemokines across several chemokine subfamilies, the viral CC chemokine inhibitor (vCCI) proteins (previously called T1͞35 kDa, also classified as type II CKBPs) produced by leporipoxviruses and orthopoxviruses bind selectively to members of the CC subfamily (16,17). vCCI proteins have been shown to be potent inhibitors of chemokine action in vitro (17) and effective anti-inflammatory agents in vivo (18). Sequence alignment of vCCI proteins from five orthopoxvirus members [rabbitpox, cowpox, vaccinia-Lister, vaccinia-Copenhagen, and variola poxvirus (the causative agent of human smallpox)] shows at least 80% identity (Fig.…”

mentioning

confidence: 99%

Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1β

Zhang

DeRider

McCornack

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

104

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Chemokines (chemotactic cytokines) comprise a large family of proteins that recruit and activate leukocytes, giving chemokines a major role in both immune response and inflammation-related diseases. The poxvirus-encoded viral CC chemokine inhibitor (vCCI) binds to many CC chemokines with high affinity, acting as a potent inhibitor of chemokine action. We have used heteronuclear multidimensional NMR to determine the structure of an orthopoxvirus vCCI in complex with a human CC chemokine, MIP-1␤ (macrophage inflammatory protein 1␤). vCCI binds to the chemokine with 1:1 stoichiometry, forming a complex of 311 aa. vCCI uses residues from its ␤-sheet II to interact with a surface of MIP-1␤ that includes residues adjacent to its N terminus, as well as residues in the 20 s region and the 40 s loop. This structure reveals the strategy used by vCCI to tightly bind numerous chemokines while retaining selectivity for the CC chemokine subfamily.inflammation ͉ protein:protein complex ͉ NMR ͉ chemokine-binding protein

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“…It has been described that vCKBP binds with high affinity to virtually all known CC chemokines, but not CXC chemokines, blocking their biological activity by competitive inhibition of chemokine interaction with their respective cellular receptors on target cells in vitro as well as in in vivo inflammatory reactions (16,17,20,21). The concomitant treatment with vCKBP significantly inhibited the LPS-induced ␥␦ T cell influx into mice pleural cavities observed 24 h after stimulation (Fig.…”

Section: Chemokine Neutralization By Vckbp Inhibits Lps-induced ␥␦mentioning

confidence: 95%

Role of Monocyte Chemotactic Protein-1/CC Chemokine Ligand 2 on γδ T Lymphocyte Trafficking during Inflammation Induced by Lipopolysaccharide orMycobacterium bovisBacille Calmette-Guérin

Penido

Vieira‐de‐Abreu

Bozza

et al. 2003

The Journal of Immunology

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γδ T lymphocytes are involved in a great variety of inflammatory and infectious responses. However, the mechanisms by which γδ T lymphocytes migrate to inflamed sites are poorly understood. In this study we investigate the role of monocyte chemotactic protein (MCP)-1 in regulating γδ T cell migration after LPS or Mycobacterium bovis bacille Calmette-Guérin (BCG) challenge. LPS-induced γδ T cell influx was significantly inhibited by either pretreatment with dexamethasone or vaccinia virus Lister 35-kDa chemokine binding protein, vCKBP, a CC chemokine neutralizing protein, suggesting a role for CC chemokines in this phenomenon. LPS stimulation increased the expression of MCP-1 mRNA and protein at the inflammation site within 6 h. It is noteworthy that LPS was unable to increase MCP-1 production or γδ T cell recruitment in C3H/HeJ, indicative of the involvement of Toll-like receptor 4. γδ T cells express MCP-1 receptor CCR2. Pretreatment with anti-MCP-1 mAb drastically inhibited LPS-induced in vivo γδ T cell mobilization. Indeed, MCP-1 knockout mice were unable to recruit γδ T cells to the pleural cavity after LPS stimulation, effect that could be restored by coadministration of MCP-1. In addition, BCG-induced γδ lymphocyte accumulation was significantly reduced in MCP-1 knockout mice when compared with wild-type mice. In conclusion, our results indicate that LPS-induced γδ T lymphocyte migration is dependent on Toll-like receptor 4 and sensitive to both dexamethasone and CC chemokine-binding protein inhibition. Moreover, by using MCP-1 neutralizing Abs and genetically deficient mice we show that LPS- and BCG-induced γδ T lymphocyte influx to the pleural cavity of mice is mainly orchestrated by the CC chemokine MCP-1.

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Local Blockade of Allergic Airway Hyperreactivity and Inflammation by the Poxvirus-Derived Pan-CC-Chemokine Inhibitor vCCI

Cited by 66 publications

References 28 publications

Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function

Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function

Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1β

Role of Monocyte Chemotactic Protein-1/CC Chemokine Ligand 2 on γδ T Lymphocyte Trafficking during Inflammation Induced by Lipopolysaccharide orMycobacterium bovisBacille Calmette-Guérin

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