Assuntos
Antígenos de Bactérias , Doenças Desmielinizantes/microbiologia , Hanseníase/microbiologia , Hanseníase/fisiopatologia , Proteínas Musculares , Mycobacterium leprae/patogenicidade , Bainha de Mielina/fisiologia , Células de Schwann/microbiologia , Células de Schwann/fisiologia , Animais , Axônios/fisiologia , Morte Celular , Diferenciação Celular , Membrana Celular/metabolismo , Técnicas de Cocultura , Proteínas do Citoesqueleto/metabolismo , Distroglicanas , Distrofina/metabolismo , Glicolipídeos/metabolismo , Humanos , Laminina/metabolismo , Hanseníase/patologia , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Mycobacterium leprae/crescimento & desenvolvimento , Mycobacterium leprae/metabolismo , Células de Schwann/citologia , UtrofinaAssuntos
Axônios/fisiologia , Bainha de Mielina/fisiologia , Células de Schwann/citologia , Células de Schwann/fisiologia , Células de Schwann/microbiologia , Diferenciação Celular , Distrofina/metabolismo , Doenças Desmielinizantes/microbiologia , Glicolipídeos/metabolismo , Glicoproteínas de Membrana/metabolismo , Hanseníase/fisiopatologia , Hanseníase/microbiologia , Hanseníase/patologia , Laminina/metabolismo , Membrana Celular/metabolismo , Mycobacterium leprae/crescimento & desenvolvimento , Mycobacterium leprae/metabolismo , Mycobacterium leprae/patogenicidade , Proteínas do Citoesqueleto/metabolismo , Técnicas de CoculturaRESUMO
Mycobacterium leprae, the causative organism of leprosy, has a unique predilection for Schwann cells, the glial cells of the peripheral nervous system. M. leprae invasion of Schwann cells leads to the neurological damage that underlies the sensory motor loss and subsequent deformity and disability associated with this disease. Recent studies have begun to elucidate the early events of M. leprae infection of Schwann cells on a molecular level, and the host and bacterial factors that determine the neural predilection of this bacterium. These advances have now provided novel insights into the mechanisms of bacterial interactions with host cells.
Assuntos
Proteínas do Citoesqueleto/metabolismo , Hanseníase/patologia , Glicoproteínas de Membrana/metabolismo , Mycobacterium leprae/patogenicidade , Nervos Periféricos/microbiologia , Células de Schwann/microbiologia , Antígenos de Bactérias/metabolismo , Parede Celular/metabolismo , Distroglicanas , Glicolipídeos/metabolismo , Humanos , Laminina/metabolismo , Hanseníase/microbiologia , Modelos Biológicos , Ligação Proteica , TropismoRESUMO
Mycobacterium leprae has the capacity to invade the peripheral nervous system and cause neuropathy. The molecular mechanisms responsible have remained unknown until recently. Identification of the endoneurial laminin-2 isoform and its receptor alpha-dystroglycan as neural targets of M. leprae has not only opened up a new area of scientific inquiry into the pathogenesis of neurological damage in leprosy, but has also revealed unexpected biological properties of these important host molecules.
Assuntos
Laminina/química , Mycobacterium leprae/patogenicidade , Nervos Periféricos/química , Doenças do Sistema Nervoso Periférico/microbiologia , Células de Schwann/microbiologia , Proteínas do Citoesqueleto/metabolismo , Distroglicanas , Humanos , Hanseníase/microbiologia , Glicoproteínas de Membrana/metabolismo , Bainha de Mielina/metabolismo , Isoformas de Proteínas/química , Estrutura Terciária de ProteínaRESUMO
alpha-Dystroglycan (alpha-DG) is a component of the dystroglycan complex, which is involved in early development and morphogenesis and in the pathogenesis of muscular dystrophies. Here, alpha-DG was shown to serve as a Schwann cell receptor for Mycobacterium leprae, the causative organism of leprosy. Mycobacterium leprae specifically bound to alpha-DG only in the presence of the G domain of the alpha2 chain of laminin-2. Native alpha-DG competitively inhibited the laminin-2-mediated M. leprae binding to primary Schwann cells. Thus, M. leprae may use linkage between the extracellular matrix and cytoskeleton through laminin-2 and alpha-DG for its interaction with Schwann cells.
Assuntos
Aderência Bacteriana , Proteínas do Citoesqueleto/metabolismo , Laminina/metabolismo , Glicoproteínas de Membrana/metabolismo , Mycobacterium leprae/metabolismo , Células de Schwann/microbiologia , Animais , Sítios de Ligação , Cálcio/fisiologia , Linhagem Celular Transformada , Células Cultivadas , Proteínas do Citoesqueleto/farmacologia , Distroglicanas , Ácido Edético/farmacologia , Glicosilação , Humanos , Laminina/química , Glicoproteínas de Membrana/farmacologia , Nervos Periféricos/química , Ratos , Receptores de Laminina/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Células de Schwann/metabolismoAssuntos
Proteínas do Citoesqueleto/metabolismo , Febre Lassa/virologia , Vírus Lassa/metabolismo , Hanseníase/microbiologia , Glicoproteínas de Membrana/metabolismo , Mycobacterium leprae/metabolismo , Animais , Aderência Bacteriana , Proteínas do Citoesqueleto/genética , Distroglicanas , Humanos , Laminina/metabolismo , Vírus da Coriomeningite Linfocítica/metabolismo , Glicoproteínas de Membrana/genética , Modelos Biológicos , Receptores Virais/metabolismo , Células de Schwann/microbiologiaAssuntos
Aderência Bacteriana , Células de Schwann/microbiologia , Febre Lassa/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Hanseníase/microbiologia , Laminina/metabolismo , Modelos Biológicos , Mycobacterium leprae/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Receptores Virais/metabolismo , Vírus Lassa/metabolismoRESUMO
In sarcoidosis, pleomorphic chromogens (PCs) occur as multivariate pigmented elements within sinusoids of lymph nodes (sinusoidal phase) and as tiny "round bodies" detectable in granulomas (generalized phase). The sinusoidal phase occurs in other conditions as well and characteristically contains yeastlike bodies also known as H-W bodies. To elucidate the antigenic profile of all variant forms, 28 cases of sarcoidosis (series A) and 14 cases of malignancy associated sinus histiocytosis (series B) were studied immunohistochemically with panels of various antibodies, including antimycobacterial MAbs specific for M tuberculosis complex (TB68, TB71), for M. leprae (MMP-I-3C3) and for cross-reactive mycobacterial antigens (F24-2-3 and F116-5, the latter recognizing superoxide dismutase). Results for series A indicate that: 1) PCs are cell-wall-deficient (CWD) mycobacterial forms belonging to M. tuberculosis complex (over 95%); 2) both phases are antigenically identical parts of the L-cycle; 3) "round bodies" of the "infective" phase have an endolysosomal evolution; 4)uncommon vacuolated forms represent a labile spheroplast stage; 5) the yeastlike bodies are specialized sinusoidal large bodies of unknown function. Results for series B show that in roughly two thirds of cases the pigmented forms are also CWD mycobacteria, have the same immunophenotype as sarcoid PCs in 35.7% of cases, have a much higher incidence of labile vacuolated forms and, finally, that malignancy associated "pseudosarcoid" granulomas do not differ antigenically from genuine sarcoid granulomas. Unlike conventional mycobacteria, PCs do not express cytoskeletal proteins consistently. Their general reactivity for HBcAg raises the possibility of phage interactions being responsible for the L-cycle since it may reflect shared epitopes between unrelated virus entities.