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Sever-Chroneos Z Krupa A Davis J Hasan M Yang CH Szeliga J Herrmann M Hussain M Geisbrecht BV Kobzik L Chroneos ZC 《The Journal of biological chemistry》2011,286(6):4854-4870
Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap(+)) but not Eap-deficient (Eap(-)) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap(+) S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly, WT mice cleared infection with Eap(+) but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap(+) S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap(-) S. aureus was impaired. Macrophages express two isoforms: SP-R210(L) and SP-R210(S). The results show that WT alveolar macrophages are distinguished by expression of SP-R210(L), whereas SR-A(-/-) alveolar macrophages are deficient in SP-R210(L) expressing only SP-R210(S). Accordingly, SR-A(-/-) mice were highly susceptible to both Eap(+) and Eap(-) S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210(L) mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A. 相似文献
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Zifa E Daniil Z Skoumi E Stavrou M Papadimitriou K Terzenidou M Kostikas K Bagiatis V Gourgoulianis KI Mamuris Z 《Molecular biology reports》2012,39(4):4697-4708
A number of studies suggest that mitochondrial dysfunction plays a role in the pathogenesis of asthma. To shed light for the
first time on the role of the mitochondrial genome in the etiology of asthma we analyzed the mitochondrial tRNA genes and
part of their flanking regions in patients with asthma compared with a set of healthy controls. We found a total of 10 mutations
in 56 out of 76 asthmatic patients. Four of these mutations were not found in the control group, five were observed at a significantly
lower frequency in controls, but none of the combinations of mutations detected in asthma patients was observed in the controls.
Furthermore, we observed that 27.6% of the asthma patients (vs. 4% of the controls) belonged to the haplogroup U (Fisher test
P = 0.00) and a positive significant correlation was found between the occurrence of the haplogroup U and the severity of the
disease (Fisher test P = 0.02). Whereas further studies in larger cohorts are needed to confirm these observations we suggest that the mitochondrial
genetic background plays a key role in asthma development. 相似文献
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A number of d-galactopyranosides bearing aromatic substituents have been prepared, and their binding to immunoglobulin J539 (Fab') has been studied. It appears that the main contribution of the 6-O-aromatic moiety to binding arises from the fact that it imparts an increased hydrophobicity to the ligand, causing a decrease in its hydration (solubility) that results in a greater free-energy of binding. In the d-galactosides having an aromatic aglycon, the phenyl group appears to partake in actual interactions with the protein. 相似文献
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Emmanuel Zissis Harry W. Diehl Hewitt G. Fletcher Nevenka Pravdić 《Carbohydrate research》1973,26(2):323-333
Dicyclohexylammonium salts of aldonic acids may be prepared from aldonolactones, as well as from metal aldonates and the free acids. Although accompanied by decomposition, their melting points are usually sharp, and these salts appear to have some potential utility for the isolation and characterization of aldonic acids.Dicyclohexylammonium 2-acetamido-2-deoxy-d-gluconate (1) has recently been described; in the course of the present investigation, it was converted into 2-acetamido-2-deoxy-d-glucose (3), confirming the configuration previously assigned to it. With aqueous dicyclohexylamine, 2-acetamido-2-deoxy-d-mannono-1,4-lactone (2) gives 1. The configuration of 2 was reconfirmed through reduction to 2-acetamido-2-deoxy-d-mannitol (4), and the optical rotations of this compound and its d-gluco isomer in acidified ammonium molybdate solution were found to be useful physical constants for distinguishing these alditols.2-Acetamido-2-deoxy-d-galactono-1,4-lactone affords a crystalline dicyclohexylammonium salt of the corresponding acid, from which the lactone may be regenerated. 相似文献