Monocyte chemoattractant protein (MCP)-1 is rapidly expressed by sympathetic ganglion neurons following axonal injury

Schreiber, R. C.; Krivacic, Kimberly; Kirby, Barbara M.; Vaccariello, Stacey A.; Wei, Tao; Ransohoff, Richard M.; Zigmond, Richard E.

doi:10.1097/00001756-200103050-00034

Cited by 57 publications

(40 citation statements)

References 22 publications

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“…MCP-1 immunoreactivity has previously been observed in injured neurons after the transection of axons of sensory, sympathetic, and facial motor neurons (21,22,34). The expression of MCP-1 is induced within hours of the injury.…”

Section: Discussionmentioning

confidence: 83%

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Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion

White

Sun

Waters

et al. 2005

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

351

372

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Neuronal hyperexcitability in both injured and adjacent uninjured neurons is associated with states of chronic injury and pain and is likely subject to neuroinflammatory processes. Chronic inflammatory responses are largely orchestrated by chemokines. One chemokine, monocyte chemoattractant protein-1 (MCP-1), in the presence of its cognate receptor, the ␤ chemokine receptor 2 (CCR2), produces neural activity in dissociated neuronal cultures of neonatal dorsal root ganglion (DRG) neurons. Using a neuropathic pain model, chronic compression of the DRG (CCD), we compared anatomically separate populations of noncompressed lumbar DRG (L3͞L6) with compressed lumbar DRG (L4͞L5) for changes in the gene expression of CCR2. In situ hybridization revealed that CCR2 mRNA was up-regulated in neurons and nonneuronal cells present in both compressed L4͞L5 and ipsilateral noncompressed L3͞L6 DRGs at postoperative day 5 (POD5). The total percentages of compressed and noncompressed neurons exhibiting CCR2 mRNA transcripts in L3, L5, and L6 DRG were 33 ؎ 3.5%, 49 ؎ 6.2%, and 41 ؎ 5.6%, respectively, and included cell bodies of small, medium, and large size. In addition, the preferred CCR2 ligand, MCP-1, was up-regulated by POD5 in both compressed L4͞L5 and noncompressed L3͞L6 DRG neurons. Application of MCP-1 to the cell bodies of the intact formerly compressed DRG in vitro produced potent excitatory effects not observed in control ganglia. MCP-1͞CCR2 signaling is directly involved with a chronic compression injury and may contribute to associated neuronal hyperexcitability and neuropathic pain.hyperalgesia ͉ nerve injury ͉ neuropathic pain ͉ peripheral sensitization I nf lammation accompanying peripheral nerve injury frequently produces neuropathic pain symptoms, such as hyperalgesia and allodynia. This hyperalgesia may reflect ongoing or ectopic changes in the excitability of neurons in both injured and adjacent uninjured dorsal root ganglion (DRG) (1). Mechanisms that may contribute to the changes in neuronal activity include altered expression of ion channels, kinases, enzymes, neuropeptides, transcription factors, neurotrophins, and͞or the de novo presence of proinflammatory mediators such as cytokines, chemokines, and their respective receptors. However, current knowledge of the modification of molecular properties in both injured and noninjured adjacent ganglia is limited.Recent studies implicate the ␤ chemokine receptor 2 (CCR2) in the development and maintenance of pain (2-4). CCR2 is a G protein-coupled receptor that is related in structure to other CCRs (5, 6) and is largely thought to be a major regulator of induced macrophage migration (7-9). CCR2 is also constitutively expressed by different types of cells in the central nervous system, including neurons (10, 11), activated astrocytes (12, 13), microglia (3), and neural progenitor cells (14,15).Most CCRs, including CCR2, bind multiple chemokines (16, 17). CCR2 binds a family of closely related ␤-chemokines (C-C) called monocyte chemoattractant proteins (MCP), of whic...

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Section: Discussionmentioning

confidence: 83%

“…For example, expression of MCP-1 can be induced by nerve injury (21,22), possibly in response to upstream regulators such as IL-6, leukemia inhibitory factor (23), or NF-B (24).…”

mentioning

confidence: 99%

Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion

White

Sun

Waters

et al. 2005

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

351

372

View full text Add to dashboard Cite

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“…Real-time RT-PCR assays were performed as previously described (29), with modifications for the detection of murine chemokines.…”

Section: Methodsmentioning

confidence: 99%

Chemokine Expression in the Central Nervous System of Mice with a Viral Disease Resembling Multiple Sclerosis: Roles of CD4⁺and CD8⁺T Cells and Viral Persistence

Ransohoff¹,

Wei²,

Pavelko

et al. 2002

J Virol

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During the first 45 days after intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV), the levels of mRNAs encoding chemokines MCP-1/CCL2, RANTES/CCL5, and IP-10/CXCL10 in the central nervous system (CNS) are closely related to the sites of virus gene expression and tissue inflammation. In the present study, these chemokines were monitored during the latter 135 days of a 6-month course of TMEVinduced disease in susceptible (PLJ) or resistant (C57BL/6) mice that possessed or lacked either CD4 ؉ or CD8 ؉ T cells. These data were additionally correlated to mouse genotype, virus persistence in the CNS, antiviral antibody titers, mortality, and the severity of neurological disease. Surprisingly, the major determinant of chemokine expression was virus persistence: the factors of susceptible or resistant genotype, severity of neuropathology, and presence or absence of regulatory T cells exerted minimal effects. Our observations indicated that chemokine expression in the CNS in this chronic viral disorder was intrinsic to the CNS innate immune response to infection and was not governed by elements of the adaptive immune system.Theiler's murine encephalomyelitis virus (TMEV) infection of the central nervous system (CNS) causes poliomyelitis that is rapidly cleared in susceptible and resistant mouse strains but is succeeded by viral persistence and inflammatory demyelination in susceptible strains of mice (7,19,21,31,33). By thorough analysis of congenic strains, the determinants of susceptibility have been mapped to both major histocompatibility complex (MHC) and non-MHC genes (19). This genetic analysis has been extended by studying TMEV disease in genetargeted mice. Recent results revealed that both CD4 and CD8 cells were required to control infection (16). CD4 ϩ cells additionally provided protection against neurological deficits that result from inflammatory demyelination (16,28).Chemokines constitute a family of peptides that act through specific high-affinity receptors (3). In concert with adhesion molecules, they define both physiological and pathological leukocyte migration patterns (5). Expression of chemokines has been defined for early time points after TMEV infection but not in chronic disease (15). Further, the regulation of TMEVinduced chemokine expression in CD4-and CD8-deficient mice has not been addressed. We used real-time reverse transcriptase PCR (RT-PCR) to evaluate CNS chemokine expression in susceptible and resistant mice, with or without deletion of CD4 or CD8 genes, across a 6-month time course of disease. These data were correlated with viral persistence, clinical deficits, mortality, and serum-neutralizing antiviral antibodies.These analyses allowed us to determine how quantitative or qualitative CNS chemokine expression was determined by the presence or absence of CD4 ϩ or CD8 ϩ T cells by susceptible or resistant genotype or by persistent viral replication. We found that quantitative and qualitative aspects of CNS chemokine expression in TMEV-infected mice were not consi...

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“…4) [21], which have the ability to polarize the infiltrated macrophages toward M2 phenotype by activation of p38 mitogen-activated protein kinase and tyrosine kinase [3], and by activation of AKT and PKA pathways, respectively [21]. In addition, CCL2/CCR2 is an important signal molecule that is enhanced upon peripheral nerve injury [53,103,117,120], and can polarize macrophages toward an M2 phenotype [112]. These findings highlight that the recruited monocytes/macrophages are polarized to M2 phenotype through a mechanism that involves apoE, collagen VI and CCL2/ CCR2, and their downstream signaling pathways.…”

Section: Role Of Macrophages In Peripheral Nerve Regenerationmentioning

confidence: 99%

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

2015

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The peripheral nervous system (PNS) has remarkable regenerative abilities after injury. Successful PNS regeneration relies on both injured axons and non-neuronal cells, including Schwann cells and immune cells. Macrophages are the most notable immune cells that play key roles in PNS injury and repair. Upon peripheral nerve injury, a large number of macrophages are accumulated at the injury sites, where they not only contribute to Wallerian degeneration, but also are educated by the local microenvironment and polarized to an anti-inflammatory phenotype (M2), thus contributing to axonal regeneration. Significant progress has been made in understanding how macrophages are educated and polarized in the injured microenvironment as well as how they contribute to axonal regeneration. Following the discussion on the main properties of macrophages and their phenotypes, in this review, we will summarize the current knowledge regarding the mechanisms of macrophage infiltration after PNS injury. Moreover, we will discuss the recent findings elucidating how macrophages are polarized to M2 phenotype in the injured PNS microenvironment, as well as the role and underlying mechanisms of macrophages in peripheral nerve injury, Wallerian degeneration and regeneration. Furthermore, we will highlight the potential application by targeting macrophages in treating peripheral nerve injury and peripheral neuropathies.

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Monocyte chemoattractant protein (MCP)-1 is rapidly expressed by sympathetic ganglion neurons following axonal injury

Cited by 57 publications

References 22 publications

Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion

Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion

Chemokine Expression in the Central Nervous System of Mice with a Viral Disease Resembling Multiple Sclerosis: Roles of CD4⁺and CD8⁺T Cells and Viral Persistence

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

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Monocyte chemoattractant protein (MCP)-1 is rapidly expressed by sympathetic ganglion neurons following axonal injury

Cited by 57 publications

References 22 publications

Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion

Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion

Chemokine Expression in the Central Nervous System of Mice with a Viral Disease Resembling Multiple Sclerosis: Roles of CD4+and CD8+T Cells and Viral Persistence

Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury

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Chemokine Expression in the Central Nervous System of Mice with a Viral Disease Resembling Multiple Sclerosis: Roles of CD4⁺and CD8⁺T Cells and Viral Persistence