RESUMO
Hematopoietic stem and progenitor cells (HSPCs) mobilization is the movement of HSPCs from the bone marrow to the peripheral blood or tissue induced by stress. HSPC mobilization is a well-known response to protect the host during infection through urgent differentiation of HSPCs to immune cells. Dengue virus (DENV) infection is known to cause stress in infected humans and the mobilizing capacity of HSPCs during DENV infection in affected patients has not been fully investigated. Here, we investigated whether DENV infection can induce HSPC mobilization and if the mobilized HSPCs are permissive to DENV infection. White blood cells (WBCs) were collected from dengue patients (DENV+) and healthy donors and analyzed by flow cytometry and plaque assay. Elevated HSPCs levels were found in the WBCs of the DENV+ group when compared to the healthy group. Mobilization of HSPCs and homing markers (skin and gut) expression decreased as the patients proceeded from dengue without symptoms (DWoWS) to severe dengue (SD). Mobilizing HSPCs were not only permissive to DENV infection, but infectious DENV could be recovered after coculture. Our results highlight the need for further investigation into HSPC mobilization or alterations of hematopoiesis during viral infections such as DENV in order to develop appropriate countermeasures.
Assuntos
Dengue , Células-Tronco Hematopoéticas , Humanos , Células-Tronco Hematopoéticas/metabolismo , Mobilização de Células-Tronco Hematopoéticas/métodos , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Dengue/metabolismoRESUMO
OBJECTIVE: To evaluate the mechanisms of bladder uric acid stone (BUAS) formation by analyzing BUAS stone matrix proteins, with mass spectrometry (MS). MATERIALS AND METHODS: Stone matrix proteins were extracted from 5 pure BUASs. The obtained proteins were analyzed with reverse phase liquid chromatography-tandem MS. The acquired data were investigated against a Swiss Prot human protein database, using Matrix Science Mascot. The identified proteins were submitted to UniProtKB website for gene ontology analysis to define their correlation. They were also submitted to Metacore platform and Kyoto Encyclopedia of Genes and Genomes website for pathway analysis. MS-determined protein expressions were validated by immunoblot. RESULTS: The liquid chromatography-tandem MS analysis identified 58-226 proteins in the 5 BUASs (450 proteins). Metacore software analysis suggests that inflammation might play an important role for BUAS formation. The analysis of endogenous metabolic pathways revealed that these proteins were categorized into glycerophospholipid or glycosphingolipid biosynthesis. Four of 5 identified proteins selected for validation, including uromodulin, S100P, Histone 4, and nucleophosmin, can be validated in the immunoblot data. CONCLUSION: Our results suggest that inflammatory process and lipid metabolism might play a role in the formation of BUAS. Whether these inflammatory responses are the etiology of stone formation or whether they result from local damage by stone irritation is uncertain.