Inhibition of Intimal Hyperplasia in Transgenic Mice Conditionally Expressing the Chemokine-Binding Protein M3

Pyo, Robert; Jensen, Kristian K.; Wiekowski, Maria; Manfra, Denise; Alcamı́, Antonio; Taubman, Mark B.; Lira, Sérgio A.

doi:10.1016/s0002-9440(10)63785-6

Cited by 44 publications

(34 citation statements)

References 65 publications

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“…Because of its strong and specifi c binding of chemokines of all four subfamilies (Parry et al, 2000;Belvončíková et al, 2008), it can serve as a potential therapeutic tool for treating diseases linked to the deregulation of chemokine network, such as diabetes mellitus type I (Martin et al, 2007(Martin et al, , 2008Lira et al, 2009). A number of other autoimmune diseases leading to chronic infl ammation could be treated with chemokine antagonists (Proudfoot et al, 2003;Pyo et al, 2004;Wu et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties

Matuskova¹,

Pančík²,

Štibrániová³

et al. 2015

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Summary. -M3 protein of murine gammaherpesvirus 68 (MHV-68) was identifi ed as a viral chemokinebinding protein 3 (vCKBP-3) capable to bind a broad spectrum of chemokines and their receptors. During both acute and latent infection MHV-68 M3 protein provides a selective advantage for the virus by inhibiting the antiviral and infl ammatory response. A unique mutation Asp307Gly was identifi ed in the M3 protein of murine gammaherpesvirus 72 (MHV-72), localized near chemokine-binding domain. Study on chemokine-binding properties of MHV-72 M3 protein purifi ed from medium of infected cells implied reduced binding to some chemokines when compared to MHV-68 M3 protein. It was suggested that the mutation in the M3 protein might be involved in the attenuation of immune response to infection with MHV-72. Recently, Escherichia coli cells were used to prepare native recombinant M3 proteins of murine gammaherpesviruses 68 and 72 (Pančík et al., 2013). In this study, we assessed the chemokine-binding properties of three M3 proteins prepared in E. coli Rosetta-gami 2 (DE3) cells, the full length M3 protein of both MHV-68 and MHV-72 and MHV-68 M3 protein truncated in the signal sequence (the fi rst 24 aa). Th ey all displayed binding activity to human chemokines CCL5 (RANTES), CXCL8 (IL-8), and CCL3 (MIP-1α). Th e truncated MHV-68 M3 protein had more than twenty times reduced binding activity to CCL5, but only about fi ve and three times reduced binding to CXCL8 and CCL3 when compared to its full length counterpart. Binding of the full length MHV-72 M3 protein to all chemokines was reduced when compared to MHV-68 M3 protein. Its binding to CCL5 and CCL3 was reduced over ten and seven times. However, its binding to CXCL8 was only slightly reduced (64.8 vs 91.8%). Th ese data implied the signifi cance of the signal sequence and also of a single mutation (at aa 307) for effi cient M3 protein binding to some chemokines.

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Section: Discussionmentioning

confidence: 99%

Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties

Matuskova¹,

Pančík²,

Štibrániová³

et al. 2015

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“…MT-1 treatment was shown to alleviate vascular pathology by inhibiting early monocyte and lymphocyte infiltration in vascular transplantation models (49). M3 has shown promise as an anti-inflammatory therapeutic in several models, including tumor rejection (50) and vascular injury (51). Islet-specific M3 expression can also prevent inflammatory recruitment, islet destruction, and subsequent diabetes in mouse insulitis models (52).…”

Section: Discussionmentioning

confidence: 99%

Rodent Herpesvirus Peru Encodes a Secreted Chemokine Decoy Receptor

Lubman

Cella

Wang

et al. 2014

J Virol

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Viruses have long been studied not only for their pathology and associated disease but also as model systems for understanding cellular and immunological processes. Rodent herpesvirus Peru (RHVP) is a recently characterized rhadinovirus related to murine gammaherpesvirus 68 (MHV68) and Kaposi's sarcoma-associated herpesvirus (KSHV) that establishes acute and latent infection in laboratory mice. RHVP encodes numerous unique proteins that we hypothesize might facilitate host immune evasion during infection. We report here that open reading frame (ORF) R17 encodes a high-affinity chemokine binding protein that broadly recognizes human and murine CC and C chemokines. The interaction of R17 with chemokines is generally characterized by rapid association kinetics, and in the case of CCL3, CCL4, CCL5, CCL24, and XCL1, extremely stable complexes are formed. Functionally, R17 potently inhibited CCL2-driven chemotaxis of the human monocytic cell line THP-1, CCL3-driven chemotaxis of peripheral blood mononuclear cells, and CCL2-mediated calcium flux. Our studies also reveal that R17 binds to glycosaminoglycans (GAGs) in a process dependent upon two BBXB motifs and that chemokine and GAG binding can occur simultaneously at distinct sites. Collectively, these studies suggest that R17 may play a role in RHVP immune evasion through the targeted sabotage of chemokine-mediated immune surveillance.

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“…Intravenous infusion of M-T7 markedly reduced intimal hyperplasia in a rabbit model of arterial injury, 64 and conditional expression of M3 inhibited intimal hyperplasia after mouse femoral arterial injury. 65 Although inhibition of MCP-1 probably accounted for a substantial portion of these effects on intimal hyperplasia, other chemokines may have contributed. In this regard, the chemokine antagonist MET-RANTES reduced neointima formation in Apoe Ϫ/Ϫ mice 62 and atherosclerotic plaque formation in LDLR Ϫ/Ϫ mice.…”

Section: Arterial Injurymentioning

confidence: 99%

Chemokines in the Pathogenesis of Vascular Disease

Charo

Taubman

2004

Circulation Research

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670

511

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Abstract-Our increasing appreciation of the importance of inflammation in vascular disease has focused attention on the molecules that direct the migration of leukocytes from the blood stream to the vessel wall. In this review, we summarize roles of the chemokines, a family of small secreted proteins that selectively recruit monocytes, neutrophils, and lymphocytes to sites of vascular injury, inflammation, and developing atherosclerosis. Chemokines induce chemotaxis through the activation of G-protein-coupled receptors, and the receptors that a given leukocyte expresses determines the chemokines to which it will respond. Monocyte chemoattractant protein 1 (MCP-1), acting through its receptor CCR2, appears to play an early and important role in the recruitment of monocytes to atherosclerotic lesions and in the formation of intimal hyperplasia after arterial injury. Acute thrombosis is an often fatal complication of atherosclerotic plaque rupture, and recent evidence suggests that MCP-1 contributes to thrombin generation and thrombus formation by generating tissue factor. Because of their critical roles in monocyte recruitment in vascular and nonvascular diseases, MCP-1 and CCR2 have become important therapeutic targets, and efforts are underway to develop potent and specific antagonists of these and related chemokines. A preponderance of evidence from clinical and experimental studies supports the notion that inflammation plays an important role in a wide range of cardiovascular diseases [1][2][3][4] and has focused attention on the signals that initiate cellular infiltration of vascular tissues. The chemokines are a family of potent chemotactic cytokines that regulate the trafficking of leukocytes and are rapidly upregulated at sites of vascular inflammation. Here, we review the role of monocyte chemoattractant protein 1 (MCP-1) and related chemokines in regulating the recruitment of monocyte/macrophages to the vessel wall and discuss how these chemokines contribute to the pathophysiology of vascular disease, with an emphasis on atherosclerosis. Chemokines and Chemokine ReceptorsChemokines (chemotactic cytokines) are small heparinbinding proteins that direct the migration of circulating leukocytes to sites of inflammation or injury. 5,6 There are Ϸ50 human chemokines, which are divided into three major families based on differences in their structure and function.The largest family is known as the CC chemokines because the first two of the four conserved cysteine residues that are characteristic of chemokines are adjacent to each other. CC chemokines tend to attract mononuclear cells and are found at sites of chronic inflammation. The most thoroughly characterized CC chemokine is MCP-1 (also known as CCL2), a potent agonist for monocytes, memory T cells, and basophils. The third family, the CX3C family, has only one known member, fractalkine (FK; or CX3CL1). FK consists of a soluble chemokine domain fused to a mucin-like stalk and a transmembrane domain. Thus, unlike other soluble chemokines, it is a type 1 tran...

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Inhibition of Intimal Hyperplasia in Transgenic Mice Conditionally Expressing the Chemokine-Binding Protein M3

Cited by 44 publications

References 65 publications

Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties

Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties

Rodent Herpesvirus Peru Encodes a Secreted Chemokine Decoy Receptor

Chemokines in the Pathogenesis of Vascular Disease

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