The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Claes H Dohlman - One of the best experts on this subject based on the ideXlab platform.
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Microglia Regulate Neuroglia Remodeling in Various Ocular and Retinal Injuries.
Journal of immunology (Baltimore Md. : 1950), 2018Co-Authors: Eleftherios I. Paschalis, James Chodosh, Fengyang Lei, Chengxin Zhou, Vassiliki Kapoulea, Reza Dana, Demetrios G Vavvas, Xiaohong Chen, Pui-chuen Hui, Claes H DohlmanAbstract:Reactive microglia and infiltrating peripheral Monocytes have been implicated in many neurodegenerative diseases of the retina and CNS. However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral Monocytes that infiltrate the retina after ocular injury in mice become permanently engrafted into the tissue, establishing a proinflammatory phenotype that promotes neurodegeneration. In this study, we show that microglia regulate the process of neuroglia remodeling during ocular injury, and their depletion results in marked upregulation of inflammatory markers, such as Il17f , Tnfsf11, Ccl4, Il1a, Ccr2, Il4, Il5 , and Csf2 in the retina, and abnormal engraftment of peripheral CCR2 + CX3CR1 + Monocytes into the retina, which is associated with increased retinal ganglion cell loss, retinal nerve fiber layer thinning, and pigmentation onto the retinal surface. Furthermore, we show that other types of ocular injuries, such as penetrating corneal trauma and ocular hypertension also cause similar changes. However, optic nerve crush injury–mediated retinal ganglion cell loss evokes neither peripheral Monocyte Response in the retina nor pigmentation, although peripheral CX3CR1 + and CCR2 + Monocytes infiltrate the optic nerve injury site and remain present for months. Our study suggests that microglia are key regulators of peripheral Monocyte infiltration and retinal pigment epithelium migration, and their depletion results in abnormal neuroglia remodeling that exacerbates neuroretinal tissue damage. This mechanism of retinal damage through neuroglia remodeling may be clinically important for the treatment of patients with ocular injuries, including surgical traumas.
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microglia regulate neuroglia remodeling in various ocular and retinal injuries
bioRxiv, 2018Co-Authors: Eleftherios I. Paschalis, James Chodosh, Chengxin Zhou, Vassiliki Kapoulea, Reza Dana, Demetrios G Vavvas, Pui-chuen Hui, Dylan Lei, Xiaohong Nancy Chen, Claes H DohlmanAbstract:Reactive microglia and infiltrating peripheral Monocytes have been implicated in many neurodegenerative diseases of the retina and central nervous system (CNS). However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral Monocytes that infiltrate the retina after ocular injury in mice become permanently engrafted into the tissue, establishing a pro-inflammatory phenotype that promotes neurodegeneration. Here, we show in mice that microglia regulate the process of neuroglia remodeling during ocular injury, and their depletion results in marked upregulation of inflammatory markers, such as Il17f, Tnfsf11, Ccl4, Il1a, Ccr2, Il4, Il5, and Csf2 in the retina, abnormal engraftment of peripheral CCR2+ CX3CR1+ Monocytes into the retina and is associated with increased retinal ganglion cell (RGC) loss, retinal nerve fiber layer thinning, and RPE65+ cell migration onto the retinal surface. Furthermore, we show that other types of ocular injuries, such as penetrating corneal trauma and ocular hypertension, also cause similar changes. However, optic nerve crush injury mediated RGC loss evokes neither peripheral Monocyte Response in the retina, nor RPE65+ cell migration, although peripheral CX3CR1+ and CCR2+ Monocytes infiltrate the optic nerve injury site and remain present for months. Our study suggests that microglia are key regulators of peripheral Monocyte infiltration and RPE migration and their depletion results in abnormal neuroglia remodeling that exacerbates neuroretinal tissue damage. This mechanism of retinal damage through neuroglia remodeling may be clinically important for the treatment of patients with ocular injuries, including surgical traumas.
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the role of microglia and peripheral Monocytes in retinal damage after corneal chemical injury
American Journal of Pathology, 2018Co-Authors: Eleftherios I. Paschalis, James Chodosh, Fengyang Lei, Chengxin Zhou, Vassiliki Kapoulea, Aristomenis Thanos, Reza Dana, Demetrios G Vavvas, Claes H DohlmanAbstract:Abstract Eyes that have suffered alkali burn to the surface are excessively susceptible to subsequent severe glaucoma and retinal ganglion cell loss, despite maximal efforts to prevent or slow down the disease. Recently, we have shown in mice and rabbits, that such retinal damage is neither mediated by the alkali itself reaching the retina nor by intraocular pressure elevation. Rather, it is caused by the up-regulation of tumor necrosis factor alpha (TNF-α) that rapidly diffuses posteriorly, causing retinal ganglion cell apoptosis and CD45 + cell activation. Here, we investigated the involvement of peripheral blood Monocytes and microglia in retinal damage. Using CX3CR1 +/EGFP ::CCR2 +/RFP reporter mice and bone marrow chimeras, we show that peripheral CX3CR1 + CD45 hi CD11b + MHC-II + Monocyte infiltrate into the retina from the optic nerve at 24 hours after the burn and release further TNF-α. A secondary source of peripheral Monocyte Response originates from a rare population of ‘patrolling' myeloid CCR2 + cells of the retina that differentiate into CX3CR1 + macrophages within hours after the injury. As a result, CX3CR1 + CD45 lo CD11b + microglia become reactive at 7 days, causing further TNF-α release. Prompt TNF-α inhibition after corneal burn suppresses Monocyte infiltration and microglia activation, and protects the retina. This study may prove relevant to other injuries of the central nervous system.
Weiyuan John Kao - One of the best experts on this subject based on the ideXlab platform.
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Fibroblasts regulate Monocyte Response to ECM‐derived matrix: The effects on Monocyte adhesion and the production of inflammatory, matrix remodeling, and growth factor proteins
Journal of biomedical materials research. Part A, 2009Co-Authors: Amy S. Chung, Weiyuan John KaoAbstract:Monocytes/macrophages and fibroblasts are recruited to the injury site and orchestrate the host Response and tissue repair. We have previously shown that polyethylene glycol (PEG)-ylated arginine-glycine-aspartic acid (RGD) sequence grafted onto an extracellular matrix (ECM)-based semi-interpenetrating network (sIPN) enhances Monocyte adhesion, and modulates subsequent gene expression and release of inflammatory and matrix remodeling factors. In this study, we investigate the direct influence of fibroblasts on Monocyte Response to this ECM mimic. Key wound-healing factors in inflammation, matrix remodeling, and regeneration were analyzed to gain insight into the interrelated role of regulation in fibroblast-Monocyte interaction. Interleukin-1alpha/−1beta (IL-1α/−1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Monocyte inflammatory protein-1alpha/−1beta (MIP-1α/−1β), transforming growth factor-alpha (TGF-α), Monocyte chemoattractant factor (MCP-1), matrix metalloproteinase-2/−9 (MMP-2/−9), vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed. Fibroblasts decreased Monocyte adhesion onto the RGD-grafted sIPN while increasing Monocyte GM-CSF on all surfaces over time except for on RGD and PHSRN-grafted sIPN at 96 h. Monocytes decreased initial fibroblast IL-1α and TGF-α, but drastically increased fibroblast MMP-2 and GM-CSF. Monocyte IL-1β, TNF-α, MIP-1β, MCP-1, MMP-9, and GM-CSF expression was increased over time in the presence of all sIPNs, and when the sIPNs were immobilized with ligands, a down-regulation of fibroblast IL-1β, MIP-1α, MIP-1β compared with unmodified sIPN was observed. When the ligand immobilized was RGD, Monocyte TGF-α, MIP-1β, and VEGF expression was increased while Monocyte GM-CSF was decreased at selected time points. These results showed a dynamic Monocyte Response to selected ECM components in the presence of fibroblasts.
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fibroblasts regulate Monocyte Response to ecm derived matrix the effects on Monocyte adhesion and the production of inflammatory matrix remodeling and growth factor proteins
Journal of Biomedical Materials Research Part A, 2009Co-Authors: Amy S. Chung, Weiyuan John KaoAbstract:Monocytes/macrophages and fibroblasts are recruited to the injury site and orchestrate the host Response and tissue repair. We have previously shown that polyethylene glycol (PEG)-ylated arginine-glycine-aspartic acid (RGD) sequence grafted onto an extracellular matrix (ECM)-based semi-interpenetrating network (sIPN) enhances Monocyte adhesion, and modulates subsequent gene expression and release of inflammatory and matrix remodeling factors. In this study, we investigate the direct influence of fibroblasts on Monocyte Response to this ECM mimic. Key wound-healing factors in inflammation, matrix remodeling, and regeneration were analyzed to gain insight into the interrelated role of regulation in fibroblast-Monocyte interaction. Interleukin-1alpha/−1beta (IL-1α/−1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Monocyte inflammatory protein-1alpha/−1beta (MIP-1α/−1β), transforming growth factor-alpha (TGF-α), Monocyte chemoattractant factor (MCP-1), matrix metalloproteinase-2/−9 (MMP-2/−9), vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed. Fibroblasts decreased Monocyte adhesion onto the RGD-grafted sIPN while increasing Monocyte GM-CSF on all surfaces over time except for on RGD and PHSRN-grafted sIPN at 96 h. Monocytes decreased initial fibroblast IL-1α and TGF-α, but drastically increased fibroblast MMP-2 and GM-CSF. Monocyte IL-1β, TNF-α, MIP-1β, MCP-1, MMP-9, and GM-CSF expression was increased over time in the presence of all sIPNs, and when the sIPNs were immobilized with ligands, a down-regulation of fibroblast IL-1β, MIP-1α, MIP-1β compared with unmodified sIPN was observed. When the ligand immobilized was RGD, Monocyte TGF-α, MIP-1β, and VEGF expression was increased while Monocyte GM-CSF was decreased at selected time points. These results showed a dynamic Monocyte Response to selected ECM components in the presence of fibroblasts.
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Fibroblasts regulate Monocyte Response to ECM-derived matrix: The effects on Monocyte adhesion and the production of inflammatory, matrix remodeling, and growth factor proteins
Journal of Biomedical Materials Research Part A, 2009Co-Authors: Amy S. Chung, Weiyuan John KaoAbstract:Monocytes/macrophages and fibroblasts are recruited to the injury site and orchestrate the host Response and tissue repair. We have previously shown that polyethylene glycol (PEG)-ylated arginine-glycine-aspartic acid (RGD) sequence grafted onto an extracellular matrix (ECM)-based semi-interpenetrating network (sIPN) enhances Monocyte adhesion, and modulates subsequent gene expression and release of inflammatory and matrix remodeling factors. In this study, we investigate the direct influence of fibroblasts on Monocyte Response to this ECM mimic. Key wound-healing factors in inflammation, matrix remodeling, and regeneration were analyzed to gain insight into the interrelated role of regulation in fibroblast-Monocyte interaction. Interleukin-lalpha/-lbeta (IL-lα/-iβ), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Monocyte inflammatory protein-lalpha/-lbeta (MIP-lα/- iβ), transforming growth factor-alpha (TGF-α), Monocyte chemoattractant factor (MCP-1), matrix metalloproteinase-2/-9 (MMP-2/-9), vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM- CSF) were analyzed. Fibroblasts decreased Monocyte adhe sion onto the RGD-grafted sIPN while increasing Monocyte GM-CSF on all surfaces over time except for on RGD and PHSRN-grafted sIPN at 96 h. Monocytes decreased initial fibroblast IL-lα and TGF-α, but drastically increased fibroblast MMP-2 and GM-CSF. Monocyte IL-iβ, TNF-α, MIP- lp, MCP-1, MMP-9, and GM-CSF expression was increased over time in the presence of all sIPNs, and when the sIPNs were immobilized with ligands, a down-regulation of fibroblast IL-iβ, MlP-lα, MIP-iβ compared with unmodified sIPN was observed. When the ligand immobilized was RGD, Monocyte TGF-α, MIP-iβ, and VEGF expression was increased while Monocyte GM-CSF was decreased at selected time points. These results showed a dynamic Monocyte Response to selected ECM components in the presence of fibroblasts. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 89A: 841-853, 2009. © 2009 Wiley Periodicals, Inc.Link_to_subscribed_fulltex
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Identification of regulatory Hck and PAI-2 proteins in the Monocyte Response to PEG-containing matrices.
Biomaterials, 2009Co-Authors: Sean T. Zuckerman, James F. Brown, Weiyuan John KaoAbstract:Abstract Mass spectrometry is a powerful proteomic tool enabling researchers to survey the global proteome of a cell. This technique has only recently been employed to investigate cell–material interactions. We had previously identified material scarcity and limited adherent cells as challenges facing mass spectrometric analysis of cell–material interactions. U937 adherent to tissue culture poly(styrene) was used as a model system for identifying proteins expressed by adherent Monocytes and analyzed by HPLC coupled offline to MALDI-ToF/ToF (LC-MALDI). We identified 645 proteins from two cation fractions of crude U937 Monocyte cell lysate. Forty three proteins of interest from the 645 were chosen based on literature searches for relevance to Monocyte–material inflammation and wound healing. Proteins such as 40S ribosomal protein S19 and tyrosyl tRNA synthetase highlight the ability of LC-MALDI to identify proteins relevant to Monocyte–material interactions that are currently unexplored. We used PEG-based semi-interpenetrating polymer networks and PEG-only hydrogels to investigate surface dependent effects on the Src family kinase Hck and plasminogen activator inhibitor-2 (PAI-2) using the pyrazolo pyrimidine small molecule inhibitor PP2 and exogenous urokinase plasminogen activator addition, respectively. Hck is well researched in cell adhesion while PAI-2 is virtually unknown in cell–material interactions. U937 on TCPS and PEG-only hydrogels secreted similar levels of inflammatory cytokines and gelatinase MMP-9. MCP-1 secretion from Monocytes on PEG-only hydrogels was Hck independent in contrast to Hck-dependent MCP-1 secretion in U937 on TCPS. Overall, U937 adherent to sIPNs secrete low levels of soluble gelatinase MMP-9, IL-1β, TNF-α, IL-6, and MCP-1 independent of Hck and PAI-2. This work demonstrates significant changes in surface dependent expression of proteins from Monocytes adherent to PEG-based materials compared to TCPS.
David R. Haynes - One of the best experts on this subject based on the ideXlab platform.
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IN VITRO HUMAN Monocyte Response TO WEAR PARTICLES OF TITANIUM ALLOY CONTAINING VANADIUM OR NIOBIUM
The Journal of bone and joint surgery. British volume, 1997Co-Authors: Donald W. Howie, Stephen E Graves, Mark J. Pearcy, David R. HaynesAbstract:Our aim was to determine whether in vitro studies would detect differences in the cellular Response to wear particles of two titanium alloys commonly used in the manufacture of joint replacement prostheses. Particles were of the order of 1 microm in diameter representative of those found adjacent to failed prostheses. Exposure of human Monocytes to titanium 6-aluminium 4- vanadium (TiAlV) at concentrations of 4 x 10(7) particles/ml produced a mean prostaglandin E2 release of 2627.6 pM; this was significantly higher than the 317.4 pM induced by titanium 6-aluminium 7-niobium alloy (TiAlNb) particles (p = 0.006). Commercially-pure titanium particles induced a release of 347.8 pM. In addition, TiAlV stimulated significantly more release of the other cell mediators, interleukin-1, tumour necrosis factor and interleukin-6. At lower concentrations of particles there was less mediator release and less obvious differences between materials. None of the materials caused significant toxicity. The levels of inflammatory mediators released by phagocytic cells in Response to wear particles may influence the amount of periprosthetic bone loss. Our findings have shown that in vitro studies can detect differences in cellular Response induced by particles of similar titanium alloys in common clinical use, although in vivo studies have shown little difference. While in vitro studies should not be used as the only form of assessment, they must be considered when assessing the relative biocompatibility of different implant materials.
Eleftherios I. Paschalis - One of the best experts on this subject based on the ideXlab platform.
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Microglia Regulate Neuroglia Remodeling in Various Ocular and Retinal Injuries.
Journal of immunology (Baltimore Md. : 1950), 2018Co-Authors: Eleftherios I. Paschalis, James Chodosh, Fengyang Lei, Chengxin Zhou, Vassiliki Kapoulea, Reza Dana, Demetrios G Vavvas, Xiaohong Chen, Pui-chuen Hui, Claes H DohlmanAbstract:Reactive microglia and infiltrating peripheral Monocytes have been implicated in many neurodegenerative diseases of the retina and CNS. However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral Monocytes that infiltrate the retina after ocular injury in mice become permanently engrafted into the tissue, establishing a proinflammatory phenotype that promotes neurodegeneration. In this study, we show that microglia regulate the process of neuroglia remodeling during ocular injury, and their depletion results in marked upregulation of inflammatory markers, such as Il17f , Tnfsf11, Ccl4, Il1a, Ccr2, Il4, Il5 , and Csf2 in the retina, and abnormal engraftment of peripheral CCR2 + CX3CR1 + Monocytes into the retina, which is associated with increased retinal ganglion cell loss, retinal nerve fiber layer thinning, and pigmentation onto the retinal surface. Furthermore, we show that other types of ocular injuries, such as penetrating corneal trauma and ocular hypertension also cause similar changes. However, optic nerve crush injury–mediated retinal ganglion cell loss evokes neither peripheral Monocyte Response in the retina nor pigmentation, although peripheral CX3CR1 + and CCR2 + Monocytes infiltrate the optic nerve injury site and remain present for months. Our study suggests that microglia are key regulators of peripheral Monocyte infiltration and retinal pigment epithelium migration, and their depletion results in abnormal neuroglia remodeling that exacerbates neuroretinal tissue damage. This mechanism of retinal damage through neuroglia remodeling may be clinically important for the treatment of patients with ocular injuries, including surgical traumas.
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microglia regulate neuroglia remodeling in various ocular and retinal injuries
bioRxiv, 2018Co-Authors: Eleftherios I. Paschalis, James Chodosh, Chengxin Zhou, Vassiliki Kapoulea, Reza Dana, Demetrios G Vavvas, Pui-chuen Hui, Dylan Lei, Xiaohong Nancy Chen, Claes H DohlmanAbstract:Reactive microglia and infiltrating peripheral Monocytes have been implicated in many neurodegenerative diseases of the retina and central nervous system (CNS). However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral Monocytes that infiltrate the retina after ocular injury in mice become permanently engrafted into the tissue, establishing a pro-inflammatory phenotype that promotes neurodegeneration. Here, we show in mice that microglia regulate the process of neuroglia remodeling during ocular injury, and their depletion results in marked upregulation of inflammatory markers, such as Il17f, Tnfsf11, Ccl4, Il1a, Ccr2, Il4, Il5, and Csf2 in the retina, abnormal engraftment of peripheral CCR2+ CX3CR1+ Monocytes into the retina and is associated with increased retinal ganglion cell (RGC) loss, retinal nerve fiber layer thinning, and RPE65+ cell migration onto the retinal surface. Furthermore, we show that other types of ocular injuries, such as penetrating corneal trauma and ocular hypertension, also cause similar changes. However, optic nerve crush injury mediated RGC loss evokes neither peripheral Monocyte Response in the retina, nor RPE65+ cell migration, although peripheral CX3CR1+ and CCR2+ Monocytes infiltrate the optic nerve injury site and remain present for months. Our study suggests that microglia are key regulators of peripheral Monocyte infiltration and RPE migration and their depletion results in abnormal neuroglia remodeling that exacerbates neuroretinal tissue damage. This mechanism of retinal damage through neuroglia remodeling may be clinically important for the treatment of patients with ocular injuries, including surgical traumas.
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the role of microglia and peripheral Monocytes in retinal damage after corneal chemical injury
American Journal of Pathology, 2018Co-Authors: Eleftherios I. Paschalis, James Chodosh, Fengyang Lei, Chengxin Zhou, Vassiliki Kapoulea, Aristomenis Thanos, Reza Dana, Demetrios G Vavvas, Claes H DohlmanAbstract:Abstract Eyes that have suffered alkali burn to the surface are excessively susceptible to subsequent severe glaucoma and retinal ganglion cell loss, despite maximal efforts to prevent or slow down the disease. Recently, we have shown in mice and rabbits, that such retinal damage is neither mediated by the alkali itself reaching the retina nor by intraocular pressure elevation. Rather, it is caused by the up-regulation of tumor necrosis factor alpha (TNF-α) that rapidly diffuses posteriorly, causing retinal ganglion cell apoptosis and CD45 + cell activation. Here, we investigated the involvement of peripheral blood Monocytes and microglia in retinal damage. Using CX3CR1 +/EGFP ::CCR2 +/RFP reporter mice and bone marrow chimeras, we show that peripheral CX3CR1 + CD45 hi CD11b + MHC-II + Monocyte infiltrate into the retina from the optic nerve at 24 hours after the burn and release further TNF-α. A secondary source of peripheral Monocyte Response originates from a rare population of ‘patrolling' myeloid CCR2 + cells of the retina that differentiate into CX3CR1 + macrophages within hours after the injury. As a result, CX3CR1 + CD45 lo CD11b + microglia become reactive at 7 days, causing further TNF-α release. Prompt TNF-α inhibition after corneal burn suppresses Monocyte infiltration and microglia activation, and protects the retina. This study may prove relevant to other injuries of the central nervous system.
Donald W. Howie - One of the best experts on this subject based on the ideXlab platform.
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IN VITRO HUMAN Monocyte Response TO WEAR PARTICLES OF TITANIUM ALLOY CONTAINING VANADIUM OR NIOBIUM
The Journal of bone and joint surgery. British volume, 1997Co-Authors: Donald W. Howie, Stephen E Graves, Mark J. Pearcy, David R. HaynesAbstract:Our aim was to determine whether in vitro studies would detect differences in the cellular Response to wear particles of two titanium alloys commonly used in the manufacture of joint replacement prostheses. Particles were of the order of 1 microm in diameter representative of those found adjacent to failed prostheses. Exposure of human Monocytes to titanium 6-aluminium 4- vanadium (TiAlV) at concentrations of 4 x 10(7) particles/ml produced a mean prostaglandin E2 release of 2627.6 pM; this was significantly higher than the 317.4 pM induced by titanium 6-aluminium 7-niobium alloy (TiAlNb) particles (p = 0.006). Commercially-pure titanium particles induced a release of 347.8 pM. In addition, TiAlV stimulated significantly more release of the other cell mediators, interleukin-1, tumour necrosis factor and interleukin-6. At lower concentrations of particles there was less mediator release and less obvious differences between materials. None of the materials caused significant toxicity. The levels of inflammatory mediators released by phagocytic cells in Response to wear particles may influence the amount of periprosthetic bone loss. Our findings have shown that in vitro studies can detect differences in cellular Response induced by particles of similar titanium alloys in common clinical use, although in vivo studies have shown little difference. While in vitro studies should not be used as the only form of assessment, they must be considered when assessing the relative biocompatibility of different implant materials.