RESUMO
INTRODUCTION: Emphysematous cystitis is a rare pathology characterized by gas bubbles within the bladder wall and lumen from gas-producing bacteria. Sepsis-associated purpura fulminans is also rare and shows poor clinical outcomes. CASE PRESENTATION: A 73-year-old man was hospitalized at a nearby hospital due to chronic subdural hematoma, symptomatic epilepsy, and diabetes mellitus. He was transferred to our hospital with fever, low blood pressure, and cyanosis of the legs, and was diagnosed with septic shock due to emphysematous cystitis with purpura fulminans. He underwent intensive treatment, including retroperitoneal drainage. Urine culture was positive for Citrobacter freundii. His general condition gradually improved and diffuse air decreased after surgery, but progressive purpuric skin necrosis became evident on the legs, which could not be salvaged. He died on the 25th hospital day. CONCLUSION: Sepsis-associated purpura fulminans caused by emphysematous cystitis shows a very poor prognosis irrespective of intensive treatment, including retroperitoneal drainage.
Assuntos
Quimiocina CCL17/sangue , Eosinofilia/sangue , Foliculite/sangue , Dermatopatias Vesiculobolhosas/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Quimiocina CCL17/imunologia , Eosinofilia/diagnóstico , Eosinofilia/imunologia , Eosinófilos/imunologia , Feminino , Foliculite/diagnóstico , Foliculite/imunologia , Humanos , Imunoglobulina E/sangue , Masculino , Dermatopatias Vesiculobolhosas/diagnóstico , Dermatopatias Vesiculobolhosas/imunologiaRESUMO
Tight junctions (TJs) are cell-cell adhesive structures that undergo continuous remodeling. We previously demonstrated that Rab13 and a junctional Rab13-binding protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) localized at TJs and mediated the endocytic recycling of the integral TJ protein occludin and the formation of functional TJs. Here, we investigated how JRAB/MICAL-L2 was targeted to TJs. Using a series of deletion mutants, we found the plasma membrane (PM)-targeting domain within JRAB/MICAL-L2. We then identified actinin-4, which was originally isolated as an actin-binding protein associated with cell motility and cancer invasion/metastasis, as a binding protein for the PM-targeting domain of JRAB/MICAL-L2, using a yeast two-hybrid system. Actinin-4 was colocalized with JRAB/MICAL-L2 at cell-cell junctions and linked JRAB/MICAL-L2 to F-actin. Although actinin-4 bound to JRAB/MICAL-L2 without Rab13, the actinin-4-JRAB/MICAL-L2 interaction was enhanced by Rab13 activation. Depletion of actinin-4 by using small interfering RNA inhibited the recruitment of occludin to TJs during the Ca(2+) switch. During the epithelial polarization after replating, JRAB/MICAL-L2 was recruited from the cytosol to cell-cell junctions. This JRAB/MICAL-L2 recruitment as well as the formation of functional TJs was delayed in actinin-4-depleted cells. These results indicate that actinin-4 is involved in recruiting JRAB/MICAL-L2 to cell-cell junctions and forming functional TJs.
Assuntos
Actinina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas dos Microfilamentos/metabolismo , Junções Íntimas/metabolismo , Actinina/genética , Actinas/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Cálcio/metabolismo , Linhagem Celular , Polaridade Celular , Cricetinae , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/genética , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Vetores Genéticos , Junções Intercelulares/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Proteínas dos Microfilamentos/genética , Ocludina , Plasmídeos/genética , Ligação Proteica , Estrutura Terciária de Proteína , RNA Interferente Pequeno/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Transfecção , Técnicas do Sistema de Duplo-Híbrido , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismoRESUMO
The assembly of tight junctions (TJs) and adherens junctions (AJs) is regulated by the transport of integral TJ and AJ proteins to and/or from the plasma membrane (PM) and it is tightly coordinated in epithelial cells. We previously reported that Rab13 and a junctional Rab13-binding protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) mediated the endocytic recycling of an integral TJ protein occludin and the formation of functional TJs. Here, we investigated the role of Rab13 and JRAB/MICAL-L2 in the transport of other integral TJ and AJ proteins claudin-1 and E-cadherin to the PM by using a Ca(2+)-switch model. Although knockdown of Rab13 specifically suppressed claudin-1 and occludin but not E-cadherin transport, knockdown of JRAB/MICAL-L2 and expression of its Rab13-binding domain (JRAB/MICAL-L2-C) inhibited claudin-1, occludin, and E-cadherin transport. We then identified Rab8 as another JRAB/MICAL-L2-C-binding protein. Knockdown of Rab8 inhibited the Rab13-independent transport of E-cadherin to the PM. Rab8 and Rab13 competed with each other for the binding to JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the perinuclear recycling/storage compartments and PM, respectively. These results suggest that the interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of AJs and TJs.