scholarly journals Strategies of Mycoplasma ovipneumoniae to evade immune clearance by alveolar macrophages

2021 ◽  
Author(s):  
Liyang Gao ◽  
Kai Zhang ◽  
Ying Zhang ◽  
Chunji Ma ◽  
Xiaoyu Zhou ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Healthy Adult ◽  
Protein Assay ◽  
Immune Clearance ◽  
Autophagy Pathway ◽  
Endosome Maturation ◽  
Related Proteins ◽  
Chronic Pneumonia ◽  
Lower Expression ◽  
Mycoplasma Ovipneumoniae

Evidences showed that M. ovipneumoniae might associate with the development and duration of chronic pneumonia. Moreover, sheep infected with M. ovipneumoniae are easily infected by other organisms, suggesting that M. ovipneumoniae may play an immunosuppressive role during infection. However, the mechanism is still poorly understood. The infection occurs in the airway, where resident alveolar macrophages first encounter M. ovipneumoniae. Therefore, primary alveolar macrophages (AMs) were collected from the lungs of healthy adult sheep, and the (iTRAQ) protein assay was used to investigate the immunosuppressive effects of M. ovipneumoniae on sheep AMs. The RAW264.7 cells were used to confirm the findings. The results showed that M. ovipneumoniae promoted higher expression of anti-apoptotic proteins and lower expression of apoptosis-related proteins in the infected AMs. Moreover, the number of infected AMs increased. However, M. ovipneumoniae reduced ATP levels in AMs and impaired late endosome maturation and phagolysosome fusion. Furthermore, M. ovipneumoniae inhibited the autophagy pathway via the Akt-mTOR axis in AMs. These findings indicated that M. ovipneumoniae had distinctive strategies to evade elimination caused by the AMs. The findings might explain the chronic infection and co-infection in sheep infected by M. ovipneumoniae.

Isolation of Mycoplasma ovipneumoniae from sheep with chronic pneumonia

1975 ◽  
Vol 97 (11) ◽  
pp. 205-206 ◽  
Author(s):  
T. Staint George ◽  
L. Carmichael
Keyword(s):  
Chronic Pneumonia ◽  
Mycoplasma Ovipneumoniae

scholarly journals Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers.

1997 ◽  
Vol 41 (6) ◽  
pp. 1399-1402 ◽  
Author(s):  
K A Rodvold ◽  
M H Gotfried ◽  
L H Danziger ◽  
R J Servi
Keyword(s):  
Steady State ◽  
Standard Deviation ◽  
Bronchoalveolar Lavage ◽  
Drug Administration ◽  
Alveolar Macrophages ◽  
Healthy Adult ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
Adult Volunteers

The steady-state concentrations of clarithromycin and azithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained in intrapulmonary samples during bronchoscopy and bronchoalveolar lavage from 40 healthy, nonsmoking adult volunteers. Mean plasma clarithromycin, 14-(R)-hydroxyclarithromycin, and azithromycin concentrations were similar to those previously reported. Clarithromycin was extensively concentrated in ELF (range of mean +/- standard deviation concentrations, 34.4 +/- 29.3 microg/ml at 4 h to 4.6 +/- 3.7 microg/ml at 24 h) and AM (480 +/- 533 microg/ml at 4 h to 99 +/- 50 microg/ml at 24 h). The concentrations of azithromycin in ELF were 1.01 +/- 0.45 microg/ml at 4 h to 1.22 +/- 0.59 microg/ml at 24 h, and those in AM were 42.7 +/- 28.7 microg/ml at 4 h to 41.7 +/- 12.1 microg/ml at 24 h. The concentrations of 14-(R)-hydroxyclarithromycin in the AM ranged from 89.3 +/- 52.8 microg/ml at 4 h to 31.3 +/- 17.7 microg/ml at 24 h. During the period of 24 h after drug administration, azithromycin and clarithromycin achieved mean concentrations in ELF and AM higher than the concomitant concentrations in plasma.

scholarly journals Structural and functional insights into the mechanism of action of plant boron transporters

2020 ◽  
Author(s):  
Savvas Saouros ◽  
Thotegowdanapalya C Mohan ◽  
Cristina Cecchetti ◽  
Silke Lehmann ◽  
Joseph D Barritt ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Growth And Development ◽  
Loss Of Function ◽  
Plant Growth And Development ◽  
Anion Exchanger 1 ◽  
Core Domain ◽  
Domain Organisation ◽  
Terminal Amino ◽  
Related Proteins ◽  
Lower Expression

Boron has essential roles in plant growth and development. BOR proteins are key in the active uptake and distribution of boron, and regulation of intracellular boron concentrations. However, their mechanism of action remains poorly studied. BOR proteins are members of the SLC4 family of transporters and thus homologues of well studied mammalian transporters including the human Anion Exchanger 1 (hAE1). Here we generated Arabidopsis thaliana BOR1 (AtBOR1) mutants based i) on known disease causing mutations of hAE1 (S466R, A500R) and ii) a loss of function mutation (D311A) identified in the yeast BOR protein, ScBOR1p. The mutants express in yeast and localise to the plasma membrane, although both S466R and A500R exhibit lower expression than the WT AtBOR1 and D311A. The D311A, S466R and A500R mutations result in a loss of boron efflux activity in a yeast bor1p knockout strain. A. thaliana plants containing these three individual mutations exhibit substantially decreased growth phenotypes both in soil and on plates under conditions of low boron. These data confirm an important role for D311 in the function of the protein and show that mutations equivalent to disease causing mutations in hAE1 have major effects in AtBOR1. We also obtained a low resolution cryo-EM structure of a BOR protein from Oryza sativa, OsBOR3. The construct used to obtain this structure lacks the 30 C-terminal amino acids but is otherwise unmodified. This structure confirms the gate and core domain organisation previously observed for related proteins, and is strongly suggestive of an inward facing conformation.

scholarly journals The Roles of Ubiquitin in Mediating Autophagy

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2025 ◽  
Author(s):  
Zhangyuan Yin ◽  
Hana Popelka ◽  
Yuchen Lei ◽  
Ying Yang ◽  
Daniel J. Klionsky
Keyword(s):  
Molecular Mechanisms ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Post Translational Modification ◽  
Subcellular Organelles ◽  
Precise Control ◽  
Ubiquitin Proteasome ◽  
Autophagy Pathway ◽  
Structural Architecture ◽  
Related Proteins

Ubiquitination, the post-translational modification essential for various intracellular processes, is implicated in multiple aspects of autophagy, the major lysosome/vacuole-dependent degradation pathway. The autophagy machinery adopted the structural architecture of ubiquitin and employs two ubiquitin-like protein conjugation systems for autophagosome biogenesis. Ubiquitin chains that are attached as labels to protein aggregates or subcellular organelles confer selectivity, allowing autophagy receptors to simultaneously bind ubiquitinated cargos and autophagy-specific ubiquitin-like modifiers (Atg8-family proteins). Moreover, there is tremendous crosstalk between autophagy and the ubiquitin-proteasome system. Ubiquitination of autophagy-related proteins or regulatory components plays significant roles in the precise control of the autophagy pathway. In this review, we summarize and discuss the molecular mechanisms and functions of ubiquitin and ubiquitination, in the process and regulation of autophagy.

scholarly journals Structural and functional insights into the mechanism of action of plant borate transporters

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Savvas Saouros ◽  
Thotegowdanapalya C. Mohan ◽  
Cristina Cecchetti ◽  
Silke Lehmann ◽  
Joseph D. Barrit ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Amino Acid Residues ◽  
Loss Of Function ◽  
Plant Growth And Development ◽  
Anion Exchanger 1 ◽  
Core Domain ◽  
Domain Organisation ◽  
Terminal Amino ◽  
Related Proteins ◽  
Lower Expression

AbstractBoron has essential roles in plant growth and development. BOR proteins are key in the active uptake and distribution of boron, and regulation of intracellular boron concentrations. However, their mechanism of action remains poorly studied. BOR proteins are homologues of the human SLC4 family of transporters, which includes well studied mammalian transporters such as the human Anion Exchanger 1 (hAE1). Here we generated Arabidopsis thaliana BOR1 (AtBOR1) variants based (i) on known disease causing mutations of hAE1 (S466R, A500R) and (ii) a loss of function mutation (D311A) identified in the yeast BOR protein, ScBOR1p. The AtBOR1 variants express in yeast and localise to the plasma membrane, although both S466R and A500R exhibit lower expression than the WT AtBOR1 and D311A. The D311A, S466R and A500R mutations result in a loss of borate efflux activity in a yeast bor1p knockout strain. A. thaliana plants containing these three individual mutations exhibit substantially decreased growth phenotypes in soil under conditions of low boron. These data confirm an important role for D311 in the function of the protein and show that mutations equivalent to disease-causing mutations in hAE1 have major effects in AtBOR1. We also obtained a low resolution cryo-EM structure of a BOR protein from Oryza sativa, OsBOR3, lacking the 30 C-terminal amino acid residues. This structure confirms the gate and core domain organisation previously observed for related proteins, and is strongly suggestive of an inward facing conformation.

scholarly journals Requirement of CRAMP for mouse macrophages to eliminate phagocytosed E. coli through an autophagy pathway

2021 ◽  
pp. jcs.252148
Author(s):  
Keqiang Chen ◽  
Teizo Yoshimura ◽  
Wanghua Gong ◽  
Cuimeng Tian ◽  
Jiaqiang Huang ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Infections ◽  
Active Form ◽  
Intracellular Bacteria ◽  
Intracellular Pathogens ◽  
Wild Type ◽  
E Coli ◽  
Mouse Macrophages ◽  
Autophagy Pathway ◽  
Related Proteins

Host-derived antimicrobial peptides play an important role in the defense against extracellular bacterial infections. However, the capacity of antimicrobial peptides derived from macrophages as potential antibacterial effectors against intracellular pathogens remains unknown. In this study, we report that normal (wild type, WT) mouse macrophages increased their expression of the cathelin-related antimicrobial peptide (CRAMP) after infection by viable E. coli or stimulation with inactivated E. coli and its product LPS, a process involving activation of NF-κB followed by protease-dependent conversion of CRAMP from an inactive precursor to an active form. The active CRAMP was required by WT macrophages to eliminate phagocytosed E. coli, with participation of autophagy-related proteins ATG5, LC3-II, and LAMP-1 as well as conjugation of the bacteria with p62. This process was impaired in CRAMP−/- macrophages resulting in retention of intracellular bacteria and fragmentation of macrophages. These results indicate CRAMP as a critical component in autophagy-mediated clearance of intracellular E. coli by mouse macrophages.

scholarly journals Requirement of the antimicrobial peptide CRAMP for macrophages to eliminate phagocytosed E. coli through an autophagy pathway

2020 ◽  
Author(s):  
Keqiang Chen ◽  
Teizo Yoshimura ◽  
Wanghua Gong ◽  
Cuimeng Tian ◽  
Jiaqiang Huang ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Bacterial Infections ◽  
Active Form ◽  
Intracellular Bacteria ◽  
Wild Type ◽  
E Coli ◽  
Mouse Macrophages ◽  
Autophagy Pathway ◽  
Related Proteins

AbstractHost-derived antimicrobial peptides play an important role in the defense against extracellular bacterial infections. However, the capacity of antimicrobial peptides derived from macrophages as potential antibacterial effectors against intracellular pathogens remains unknown. In this study, we report that normal (wild type, WT) mouse macrophages increased their expression of the cathelicidin-related antimicrobial peptide (CRAMP) after infection by viable E. coli or stimulation with inactivated E. coli and its product LPS, a process involving activation of NF-κB followed by protease-dependent conversion of CRAMP from an inactive precursor to an active form. The active CRAMP was required by WT macrophages to eliminate phagocytosed E. coli, with participation of autophagy-related proteins ATG5, LC3-II, and LAMP-1 as well as conjugation of the bacteria with p62. The autophagy-mediated elimination of E. coli was impaired in CRAMP−/− macrophages resulting in retention of intracellular bacteria and fragmentation of macrophages. These results indicate CRAMP as a critical component in autophagy-mediated clearance of intracellular E. coli by macrophages.

scholarly journals Intracellular Expression of Neurotrophic Factors in Mononuclear Cells of Cord Blood and G-CSF-Mobilized Peripheral Blood As a Potential Source for Cellular Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5121-5121
Author(s):  
Young-Ho Lee ◽  
Hani Koh ◽  
Kyoujung Hwang
Keyword(s):  
Inflammatory Cytokines ◽  
Neurotrophic Factors ◽  
Mononuclear Cells ◽  
Cellular Therapy ◽  
Healthy Adult ◽  
Healthy Adults ◽  
Potential Source ◽  
Intracellular Expression ◽  
Mobilized Peripheral Blood ◽  
Lower Expression

Abstract Purpose: To investigate a possible therapeutic mechanism for cell therapy in the field of neurological disorders using mobilized peripheral blood mononuclear cells (mPBMCs), we compared the expression of inflammatory cytokines and neurotrophic factors in PBMCs and mPBMCs from children with cerebral palsy (CP) to those from healthy adult donors and to cord blood (CB) donated from healthy newborns. Methods: We evaluated the intracellular expression of neurotrophic factors and inflammatory cytokines in PBMCs and mPBMCs from 14 CP children and 14 healthy adult volunteer donors as well as CB mononuclear cells (CB-MNCs) donated from healthy newborns. For mPBMC, granulocyte colony stimulating factor (G-CSF, 10μg/kg/day) was administered subcutaneously for five consecutive days, and apheresis was performed on the fifth day to collect mPBMC via a central venous catheter. Both PBMC collected prior to G-CSF administration and apheresed mPBMC were cryopreserved. We performed flow cytometric analysis with intracellular staining for various cytokines after thawing PBMCs and mPBMCs as well as CBs. Results: No significant differences in expression of neurotrophic factors were found between PBMC and mPBMC. However, in cells from CP children, the expression of IL-6 was significantly increased in mPBMC as compared to PBMC, and IL-3 was significantly decreased in mPBMC as compared to PBMC. In healthy adults, the expression of both IL-1β and IL-6 were significantly increased in mPBMC as compared to PBMC. The expression of BDNF in mPBMC from CP children was significantly higher than in CB or mPBMC from healthy adults. The expression of G-CSF in mPBMC from CP children was comparable to that in CB but significantly higher than in mPBMC from healthy adults. Lower expression of IL-1β, IL-3, and IL-6 and higher expression of IL-8 and IL-9 was observed from CB and mPBMCs from CP children rather than in healthy adults. Lower expression of IL-1β, and higher expression of IL-8 was observed from mPBMCs from CP children rather than in healthy adults. Conclusion: The altered expression of neurotrophic factors and anti-inflammatory cytokines in mPBMC in CP children and CB from healthy children could provide a new potential source for cellular therapy for individuals with neurologic diseases. Disclosures Lee: Korea Healthcare Technology R&D Project (A101712), Ministry for Health & Welfare, Republic of Korea: Research Funding.

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