Fractalkine and CX3CR1 are involved in the migration of intravenously grafted human bone marrow stromal cells toward ischemic brain lesion in rats

Zhu, Jie; Zhou, Zhujuan; Liu, Yong; Zheng, Jie

doi:10.1016/j.brainres.2009.06.068

Cited by 37 publications

(27 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…• Fractalkine/CX3CL1 downstream signaling is functional in the trafficking of transplanted (CX3CR1-expressing) rat and human MSCs in rats with hypoglossal nerve injury and MCAo, respectively (Ji et al, 2004;Zhu et al, 2009);…”

Section: Homing and Extravasationmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

111

109

View full text Add to dashboard Cite

Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

show abstract

Section: Homing and Extravasationmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

111

109

View full text Add to dashboard Cite

show abstract

“…After transient brain ischemia and during excitotoxic insult, neurons release soluble fractalkine/CX3CL1 (Chapman et al, 2000;Tarozzo et al, 2002;Zhu et al, 2009), a chemokine whose specific receptor CX3CR1 is expressed by microglia (Harrison et al, 1998). CX3CL1 reduces microglia toxicity and, consequently, neuronal damage both in vitro and in vivo models of neuropathologies and brain inflammation (Zujovic et al, 2000;Mizuno et al, 2003;Cardona et al, 2006;Bhaskar et al, 2010;Noda et al, 2011;Pabon et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

CX3CL1 Is Neuroprotective in Permanent Focal Cerebral Ischemia in Rodents

Cipriani¹,

Villa²,

Chece³

et al. 2011

J. Neurosci.

170

152

View full text Add to dashboard Cite

The chemokine CX3CL1 and its receptor CX3CR1 are constitutively expressed in the nervous system. In this study, we used in vivo murine models of permanent middle cerebral artery occlusion (pMCAO) to investigate the protective potential of CX3CL1. We report that exogenous CX3CL1 reduced ischemia-induced cerebral infarct size, neurological deficits, and caspase-3 activation. CX3CL1-induced neuroprotective effects were long lasting, being observed up to 50 d after pMCAO in rats. The neuroprotective action of CX3CL1 in different models of brain injuries is mediated by its inhibitory activity on microglia and, in vitro, requires the activation of adenosine receptor 1 (A 1 R). We show that, in the presence of the A 1 R antagonist 1,3-dipropyl-8-cyclopentylxanthine and in A 1 R ؊/؊ mice, the neuroprotective effect of CX3CL1 on pMCAO was abolished, indicating the critical importance of the adenosine system in CX3CL1 protection also in vivo. In apparent contrast with the above reported data but in agreement with previous findings, cx3cl1 ؊/؊ and cx3cr1 GFP/GFP mice, respectively, deficient in CX3CL1 or CX3CR1, had less severe brain injury on pMCAO, and the administration of exogenous CX3CL1 increased brain damage in cx3cl1 ؊/؊ ischemic mice. We also report that CX3CL1 induced a different phagocytic activity in wild type and cx3cl1 ؊/؊ microglia in vitro during cotreatment with the medium conditioned by neurons damaged by oxygenglucose deprivation. Together, these data suggest that acute administration of CX3CL1 reduces ischemic damage via an adenosinedependent mechanism and that the absence of constitutive CX3CL1-CX3CR1 signaling changes the outcome of microglia-mediated effects during CX3CL1 administration to ischemic brain.

show abstract

“…Damaged neurons respond to neurotoxic insults releasing soluble factors that can be sensed by surrounding glia: CX3CL1, a chemokine selectively expressed by neurons in the nervous system, is one of such mediators being upregulated (Tarozzo et al, 2002; Zhu et al, 2009), cleaved and released upon ischemia and excitotoxic insult (Chapman et al, 2000; Limatola et al, 2005; Noda et al, 2011 ) and being able to drive neuroprotection (Limatola et al, 2005; Lauro et al, 2010; Cipriani et al, 2011). We reported here that, upon CX3CL1 stimulation, glial cells produce and release CXCL16, important for CX3CL1 neuroprotective effect.…”

Section: Discussionmentioning

confidence: 99%

Trasmembrane chemokines CX3CL1 and CXCL16 drive interplay between neurons, microglia and astrocytes to counteract pMCAO and excitotoxic neuronal death

Rosito

Lauro

Chece

et al. 2014

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Upon noxious insults, cells of the brain parenchyma activate endogenous self-protective mechanisms to counteract brain damage. Interplay between microglia and astrocytes can be determinant to build a physiological response to noxious stimuli arisen from injury or stress, thus understanding the cross talk between microglia and astrocytes would be helpful to elucidate the role of glial cells in endogenous protective mechanisms and might contribute to the development of new strategy to mobilize such program and reduce brain cell death. Here we demonstrate that chemokines CX3CL1 and CXCL16 are molecular players that synergistically drive cross-talk between neurons, microglia and astrocytes to promote physiological neuroprotective mechanisms that counteract neuronal cell death due to ischemic and excitotoxic insults. In an in vivo model of permanent middle cerebral artery occlusion (pMCAO) we found that exogenous administration of soluble CXCL16 reduces ischemic volume and that, upon pMCAO, endogenous CXCL16 signaling restrains brain damage, being ischemic volume reduced in mice that lack CXCL16 receptor. We demonstrated that CX3CL1, acting on microglia, elicits CXCL16 release from glia and this is important to induce neroprotection since lack of CXCL16 signaling impairs CX3CL1 neuroprotection against both in vitro Glu-excitotoxic insult and pMCAO. Moreover the activity of adenosine receptor A3R and the astrocytic release of CCL2 play also a role in trasmembrane chemokine neuroprotective effect, since their inactivation reduces CX3CL1- and CXCL16 induced neuroprotection.

show abstract

Fractalkine and CX3CR1 are involved in the migration of intravenously grafted human bone marrow stromal cells toward ischemic brain lesion in rats

Cited by 37 publications

References 40 publications

How stem cells speak with host immune cells in inflammatory brain diseases

How stem cells speak with host immune cells in inflammatory brain diseases

CX3CL1 Is Neuroprotective in Permanent Focal Cerebral Ischemia in Rodents

Trasmembrane chemokines CX3CL1 and CXCL16 drive interplay between neurons, microglia and astrocytes to counteract pMCAO and excitotoxic neuronal death

Contact Info

Product

Resources

About