Fc? receptor-mediated inflammation inhibits axon regeneration.
Autor(es): Zhang Gang.; Bogdanova Nataliia.; Gao Tong.; Song Julia J.; Cragg Mark S.; Glennie Martin J.; Sheikh Kazim A.
Resumo: Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fc? receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fc? receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fc? receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fc? receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.
Imprenta: PloS One, v. 9, n. 2, 2014
Identificador do objeto digital: 10.1371/journal.pone.0088703
Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Cytopathology ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Inflammation ; Guillain-Barre Syndrome - Real Time PCR ; Guillain-Barre Syndrome - Molecular screening ; Guillain-Barre Syndrome - Vaccine ; Guillain-Barre Syndrome - Immunology
Data de publicação: 2014
Fatal error: Uncaught TypeError: pg_num_rows(): Argument #1 ($result) must be of type resource, bool given in /var/www/html/manager/count_visitas_wp.ini:37 Stack trace: #0 /var/www/html/manager/count_visitas_wp.ini(37): pg_num_rows() #1 /var/www/html/manager/count_visitas_wp.ini(6): visitacheck() #2 /var/www/html/bd/wp-content/plugins/insert-php/includes/shortcodes/shortcode-php.php(60) : eval()'d code(205): include('...') #3 /var/www/html/bd/wp-content/plugins/insert-php/includes/shortcodes/shortcode-php.php(60): eval() #4 /var/www/html/bd/wp-content/plugins/insert-php/libs/factory/shortcodes/shortcode.class.php(289): WINP_SnippetShortcodePhp->html() #5 /var/www/html/bd/wp-content/plugins/insert-php/libs/factory/shortcodes/shortcodes.php(98): Wbcr_FactoryShortcodes335_Shortcode->render() #6 /var/www/html/bd/wp-includes/shortcodes.php(434): Wbcr_FactoryShortcodes335_ShortcodeManager->__call() #7 [internal function]: do_shortcode_tag() #8 /var/www/html/bd/wp-includes/shortcodes.php(273): preg_replace_callback() #9 /var/www/html/bd/wp-content/plugins/elementor/includes/widgets/shortcode.php(141): do_shortcode() #10 /var/www/html/bd/wp-content/plugins/elementor/includes/base/controls-stack.php(2374): Elementor\Widget_Shortcode->render() #11 /var/www/html/bd/wp-content/plugins/elementor/includes/base/widget-base.php(636): Elementor\Controls_Stack->render_by_mode() #12 /var/www/html/bd/wp-content/plugins/elementor/includes/base/widget-base.php(774): Elementor\Widget_Base->render_content() #13 /var/www/html/bd/wp-content/plugins/elementor/includes/base/element-base.php(482): Elementor\Widget_Base->print_content() #14 /var/www/html/bd/wp-content/plugins/elementor/includes/base/element-base.php(1443): Elementor\Element_Base->print_element() #15 /var/www/html/bd/wp-content/plugins/elementor/includes/base/element-base.php(482): Elementor\Element_Base->print_content() #16 /var/www/html/bd/wp-content/plugins/elementor/includes/base/element-base.php(1443): Elementor\Element_Base->print_element() #17 /var/www/html/bd/wp-content/plugins/elementor/includes/base/element-base.php(482): Elementor\Element_Base->print_content() #18 /var/www/html/bd/wp-content/plugins/elementor/core/base/document.php(1887): Elementor\Element_Base->print_element() #19 /var/www/html/bd/wp-content/plugins/elementor/core/base/document.php(1803): Elementor\Core\Base\Document->do_print_elements() #20 /var/www/html/bd/wp-content/plugins/elementor/core/base/document.php(1202): Elementor\Core\Base\Document->print_elements() #21 /var/www/html/bd/wp-content/plugins/elementor/includes/frontend.php(1203): Elementor\Core\Base\Document->print_elements_with_wrapper() #22 /var/www/html/bd/wp-content/plugins/elementor/includes/frontend.php(1098): Elementor\Frontend->get_builder_content() #23 /var/www/html/bd/wp-includes/class-wp-hook.php(324): Elementor\Frontend->apply_builder_in_content() #24 /var/www/html/bd/wp-includes/plugin.php(205): WP_Hook->apply_filters() #25 /var/www/html/bd/wp-includes/post-template.php(256): apply_filters() #26 /var/www/html/bd/wp-content/themes/startkit/page.php(26): the_content() #27 /var/www/html/bd/wp-includes/template-loader.php(106): include('...') #28 /var/www/html/bd/wp-blog-header.php(19): require_once('...') #29 /var/www/html/bd/index.php(17): require('...') #30 {main} thrown in /var/www/html/manager/count_visitas_wp.ini on line 37