Complement Depletion Reduces Macrophage Infiltration and Activation during Wallerian Degeneration and Axonal Regeneration

Dailey, Andrew T.; Avellino, Anthony M.; Benthem, Lambertus; Silver, Jerry; Kliot, Michel

doi:10.1523/jneurosci.18-17-06713.1998

Cited by 125 publications

(78 citation statements)

References 60 publications

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“…The genes encoding the common macrophage marker CD68 and the antigen recognized by the macrophage-specific antibody F4͞80 (Emr1) were selected as anchors to monitor macrophage infiltration. The expression level of these two genes gradually increases following injury, peaks after 7 days, then declines toward basal levels, consistent with previous observations of macrophage infiltration into injured nerve (16,21). Indeed, 11 of the 14 known genes identified were related to macrophages or the inflammatory process, including CSF-1 receptor, a well characterized macrophage marker (Fig.…”

Section: Resultssupporting

confidence: 89%

Deciphering peripheral nerve myelination by using Schwann cell expression profiling

Nagarajan

Le²,

Mahoney³

et al. 2002

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

124

131

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Although mutations in multiple genes are associated with inherited demyelinating neuropathies, the molecular components and pathways crucial for myelination remain largely unknown. To approach this question, we performed genome-wide expression analysis in several paradigms where the status of peripheral nerve myelination is dynamically changing. Anchor gene correlation analysis, a form of microarray analysis that integrates functional information, using correlation-based clustering, with a statistically rigorous test, the Westfall and Young step-down algorithm, was applied to this data set. Biological pathways active in myelination, genes encoding proteins involved in myelin synthesis, and genes whose mutation results in myelination defects were identified. Many known genes and previously uncharacterized ESTs not heretofore associated with myelination were also identified. One of these ESTs, MASR (myelin-associated SUR4 protein), encodes a member of the SUR4 family of fatty acid desaturases, enzymes involved in elongation of very long chain fatty acids. Its specific localization in myelinating Schwann cells indicates a crucial role for MASR in normal myelin lipid synthesis.

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Section: Resultssupporting

confidence: 89%

Deciphering peripheral nerve myelination by using Schwann cell expression profiling

Nagarajan

Le²,

Mahoney³

et al. 2002

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

124

131

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“…At 4 d (for macrophage and axon staining) or 7 d (for axon staining) after the nerve crush injury, adenovirus-infected sciatic nerves were removed and frozen in a block of Tissue Tek OCT. Serial 8 m longitudinal cryostat sections were cut and subjected to immunohistochemical staining as described previously (Dailey et al, 1998). ED-1 (1:5000; Serotec) or 2H3 (1:50; cell supernatant of 2H3 mouse hybridoma; Developmental Studies Hybridoma Bank, University of Iowa, Iowa City, IA) antibodies were used as primary antibodies for staining the macrophages or regenerating axons, respectively.…”

Section: Methodsmentioning

confidence: 99%

Pancreatitis-Associated Protein-III Is a Novel Macrophage Chemoattractant Implicated in Nerve Regeneration

et al. 2006

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Circulating macrophages are recruited to degenerating nerves in response to nerve injury to remove myelin and axonal debris, a process that is crucial for successful nerve regeneration. In this study, we demonstrate that pancreatitis-associated protein (PAP)-III is a macrophage chemoattractant that is induced in and released from injured nerves. In vitro experiments revealed that PAP-III possessed a strong macrophage chemoattractant activity that was comparable with that of monocyte chemoattractant protein-1. In addition, gene knockdown via adenovirus-mediated small interference RNA expression in isolated sciatic nerves successfully suppressed PAP-III expression and its macrophage chemoattractant activity. Furthermore, overexpression or knockdown of the PAP-III gene in crushed sciatic nerves in rats resulted in acceleration or retardation of macrophage recruitment and subsequent nerve regeneration, respectively. Collectively, our results demonstrate that PAP-III is a novel macrophage chemoattractant that is involved in peripheral nerve regeneration and further provide new insights into Schwann cell-macrophage interactions and therapeutic interventions.

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“…Using this method, we could obtain highly purified macrophages (80%). The identity of the macrophages was verified using an anti-ED-1 antibody (Serotec, Oxford, UK) (Dailey et al, 1998).…”

Section: Methodsmentioning

confidence: 99%

Oxidized Galectin-1 Stimulates Macrophages to Promote Axonal Regeneration in Peripheral Nerves after Axotomy

et al. 2004

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Various neurotrophic factors that promote axonal regeneration have been investigated in vivo, but the signals that prompt neurons to send out processes in peripheral nerves after axotomy are not well understood. Previously, we have shown oxidized galectin-1 (GAL-1/Ox) promotes initial axonal growth after axotomy in peripheral nerves. However, the mechanism by which GAL-1/Ox promotes axonal regeneration remains unclear and is the subject of the present study. To identify possible target cells of GAL-1/Ox, a fluorescently labeled recombinant human GAL-1/Ox (rhGAL-1/Ox) was incubated with DRG neurons, Schwann cells, and intraperitoneal macrophages from adult rats. Only the cell surfaces of intraperitoneal macrophages bound the rhGAL-1/Ox, suggesting that these cells possess a receptor for GAL-1/Ox. Experiments examining tyrosine phosphorylation revealed that rhGAL-1/Ox stimulated changes in signal transduction pathways in these macrophages. These changes caused macrophages to secrete an axonal growth-promoting factor. This was demonstrated when conditioned media of macrophages stimulated with rhGAL-1/Ox in 48 hr culture strongly enhanced axonal regeneration from transected-nerve sites of DRG explants. Furthermore, activated macrophage-conditioned media also improved Schwann cell migration from the transected-nerve sites. From these results, we propose that axonal regeneration occurs in axotomized peripheral nerves as a result of cytosolic reduced galectin-1 being released from Schwann cells and injured axons, which then becomes oxidized in the extracellular space. Oxidized galectin-1 then stimulates macrophages to secrete a factor that promotes axonal growth and Schwann cell migration, thus enhancing peripheral nerve regeneration.

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Complement Depletion Reduces Macrophage Infiltration and Activation during Wallerian Degeneration and Axonal Regeneration

Cited by 125 publications

References 60 publications

Deciphering peripheral nerve myelination by using Schwann cell expression profiling

Deciphering peripheral nerve myelination by using Schwann cell expression profiling

Pancreatitis-Associated Protein-III Is a Novel Macrophage Chemoattractant Implicated in Nerve Regeneration

Oxidized Galectin-1 Stimulates Macrophages to Promote Axonal Regeneration in Peripheral Nerves after Axotomy

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