Mannan-binding lectin at supraphysiological concentrations inhibits differentiation of dendritic cells from human CD14+ monocytes.

Mannan-binding lectin (MBL), a circulating C-type lectin, is an important member of the defense collagen family. It exhibits a high potential for recognizing broad categories of pathogen-associated molecular patterns and initiating complement cascade responses. DCs are well-known specialist antigen-presenting cells that significantly trigger specific T cell-mediated immune responses. In our previous study, it was observed that high concentrations of MBL significantly attenuate LPS-induced maturation of monocyte-derived DCs (MoDCs). In the current study, it was postulated that MBL at similar supraphysiological concentrations would affect early differentiation of MoDCs in some way. CD14(+) monocytes from human peripheral blood mononuclear cells were cultured with granulocyte-macrophage colony-stimulating factor and IL-4 in the presence or absence of physiological (1 µg/mL) and supraphysiological concentrations (20 µg/mL) of MBL protein, respectively. Phenotypic analysis indicated that the differentiated DCs incubated with high concentrations of MBL expressed MHC class II and costimulatory molecules (e.g., CD80 and CD40) more weakly than did control groups. The secretion of IL-10 and IL-6 increased markedly, whereas their mixed lymphocyte reaction-stimulating capacity decreased. Members of the signal transducer and activator of transcription family were also found to be differentially regulated. Thus, beyond the role of MBL as an opsonin, our data reveal a possible inhibitory effect of MBL at high concentrations in monocyte-DC transition, which probably provides one way of regulating adaptive immune responses by strict regulation of DCs, making MBL a better prospect for controlling relevant pathological events such as autoimmune diseases.

Clinical value of contrast-enhanced ultrasound in transthoracic biopsy of malignant anterior mediastinal masses.

BACKGROUND: Given low incidence and high heterogeneity, the treatment strategies of anterior mediastinal masses (AMMs) are diverse based on pathology. The purpose of the study is to evaluate the usefulness of contrast-enhanced ultrasound (CEUS) in transthoracic biopsy of malignant AMMs when compared with that of ultrasound (US) alone and to screen lesions that are more suitable for CEUS evaluation and guidance. METHODS: We reviewed all the US- and CEUS-guided transthoracic core needle biopsy (CNB) of AMMs performed in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between July 2013 and April 2019. A total of 68 patients (mean age 36 years; male-female ration 1.6:1) who were suspected with malignant AMMs were enrolled in the study. Among them, 20 patients received pre-biopsy CEUS examination (CEUS group); 48 patients underwent conventional US examination and guidance (US group). Demographic, radiologic, pathologic, medical records, and biopsy procedure details were retrospectively reviewed and compared between the two groups. RESULTS: The display of internal necrosis areas was significantly improved when compared with that of the conventional US (70%, 30%; P=0.008). Specifically, CEUS improved the diagnostic accuracy of US-guided transthoracic biopsy (95.0%, 79.2%; P=0.210) and especially for AMMs exceeding 10 cm (100%, 68.2%; P=0.040) and carcinoma (100%, 0%; P=0.048). The number of punctures in US group and CEUS group was 2.6 and 4.4 times, respectively (P<0.001). In case of similar number of punctures (1 to 3 times), CEUS improved diagnostic accuracy when compared to that of the conventional US (100%, 75%; P=0.486). The technical success rate was 100% (68/68). In both groups, patients did not exhibit symptomatic complications such as bleeding, pneumothorax, or hemoptysis after the biopsy. CONCLUSIONS: The application of CEUS in transthoracic biopsy of malignant AMMs improved diagnostic accuracy when compared with conventional US and especially played more important role in lesions exceeding 10 cm and presumptive clinical carcinoma.

The structure of a complex of the lactonohydrolase zearalenone hydrolase with the hydrolysis product of zearalenone at 1.60†Šresolution.

Zearalenone hydrolase (ZHD) is an α/ß-hydrolase that detoxifies and degrades the lactone zearalenone (ZEN), a naturally occurring oestrogenic mycotoxin that contaminates crops. Several apoenzyme and enzyme-substrate complex structures have been reported in the resolution range 2.4-2.6 Å. However, the properties and mechanism of this enzyme are not yet fully understood. Here, a 1.60 Šresolution structure of a ZHD-product complex is reported which was determined from a C-terminally His6-tagged ZHD crystal soaked with 2 mM ZEN for 30 min. It shows that after the lactone-bond cleavage, the phenol-ring region moves closer to residues Leu132, Tyr187 and Pro188, while the lactone-ring region barely moves. Comparisons of the ZHD-substrate and ZHD-product structures show that the hydrophilic interactions change, especially Trp183 Nℇ1, which shifts from contacting O2 to O12', suggesting that Trp183 is responsible for the unidirectional translational movement of the phenol ring. This structure provides information on the final stage of the catalytic mechanism of zearalenone hydrolysis.

[Human soluble dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin inhibits phagocytosis of Staphylococcus aureus by immature dendritic cells].

OBJECTIVE: To study the effect and mechanism of soluble dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (sDC-SIGN) on the phagocytosis of Staphylococcus aureus (S. aureus) by immature dendritic cells (imDCs). METHODS: Flow cytometry was employed to examine the effect of sDC-SIGN on the phagocytosis of S. aureus by imDCs. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the binging of sDC-SIGN to S. aureus, lipoteichoic acid (LTA) and lipopolysaccharides (LPS) and investigate the effect of the ligands mannan and LTA and anti-DC-SIGN antibodies 1C6 and 4H3 on the binging of sDC-SIGN to S. aureus. RESULTS: sDC-SIGN inhibited the phagocytosis of S. aureus by imDCs. sDC-SIGN bound to S. aureus in a Ca(2+)-dependent manner. sDC-SIGN concentration-dependently bound to LTA, but not to LTA, and the binging of sDC-SIGN to S. aureus was blocked by mannan, LTA, 1C6 and 4H3. CONCLUSION: sDC-SIGN preferentially binds to the carbohydrate constituents on S. aureus to affect the binding between membrane-bound DC-SIGN and S. aureus, thus suppressing the phagocytosis of S. aureus by imDCs.