Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human Sinusoidal Endothelium Is Associated with Decreased Expression of CD13

Resheq, Yazid J.; Menzner, Ann-Katrin; Bosch, Johanna L.; Tickle, Joseph; Li, Ka-Kit; Wilhelm, A; Hepburn, Elizabeth; Murihead, Gillian; Ward, Steve; Curbishley, Stuart M.; Zimmermann, Henning W.; Bruns, Tony; Gilbert, Daniel F.; Tripal, Philipp; Mackensen, Andréas; Adams, David H.; Weston, Chris J.

doi:10.4049/jimmunol.1600466

Cited by 10 publications

(6 citation statements)

References 49 publications

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“…These expression patterns of fibronectin and VEGFR1 + VLA-4 + clusters foster a supportive microenvironment for incoming LLC or melanoma B12 cells and dictate organ-specific tumor spread (4). Blocking VLA-4 reduces tissue infiltration of M-MDSCs through inhibiting adherence to the apical side of the endothelium during the pathogenic process underlying hepatic inflammation (74). These results suggest that VLA-4 is a key molecule that regulates MDSC infiltration into tissues and may serve as an important target for blocking PMN formation.…”

Section: Regulation Of Mdsc Recruitment and Activation In The Pmnmentioning

confidence: 99%

MDSCs: Key Criminals of Tumor Pre-metastatic Niche Formation

et al. 2019

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The emergence of disseminated metastases remains the primary cause of mortality in cancer patients. Formation of the pre-metastatic niche (PMN), which precedes the establishment of tumor lesions, is critical for metastases. Bone marrow-derived myeloid cells (BMDCs) are indispensable for PMN formation. Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells that accumulate in patients with cancer and appear in the early PMN. The mechanisms by which MDSCs establish the pre-metastatic microenvironment in distant organs are largely unknown, although MDSCs play an essential role in metastasis. Here, we summarize the key factors associated with the recruitment and activation of MDSCs in the PMN and review the mechanisms by which MDSCs regulate PMN formation and evolution. Finally, we predict the potential value of MDSCs in PMN detection and therapy.

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Section: Regulation Of Mdsc Recruitment and Activation In The Pmnmentioning

confidence: 99%

MDSCs: Key Criminals of Tumor Pre-metastatic Niche Formation

et al. 2019

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“…S1A) compared to sham. As CD13 plays a role in trans-migration [ 27 , 42 ], we examined brain CD13 + Ly6G neutrophils and Ly6c hi inflammatory monocytes, early responders after ischemic stroke. The percentage of infiltrated CD13 + Ly6G neutrophils and Ly6C hi monocytes was higher in the animals that underwent MCAO suggesting a trans-migratory role of CD13 after stroke (Additional file 1 : Fig.…”

Section: Resultsmentioning

confidence: 99%

CD13 facilitates immune cell migration and aggravates acute injury but promotes chronic post-stroke recovery

Nguyen,

Mohan,

Pandya

et al. 2023

J Neuroinflammation

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Introduction Acute stroke leads to the activation of myeloid cells. These cells express adhesion molecules and transmigrate to the brain, thereby aggravating injury. Chronically after stroke, repair processes, including angiogenesis, are activated and enhance post-stroke recovery. Activated myeloid cells express CD13, which facilitates their migration into the site of injury. However, angiogenic blood vessels which play a role in recovery also express CD13. Overall, the specific contribution of CD13 to acute and chronic stroke outcomes is unknown. Methods CD13 expression was estimated in both mice and humans after the ischemic stroke. Young (8–12 weeks) male wild-type and global CD13 knockout (KO) mice were used for this study. Mice underwent 60 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. For acute studies, the mice were euthanized at either 24- or 72 h post-stroke. For chronic studies, the Y-maze, Barnes maze, and the open field were performed on day 7 and day 28 post-stroke. Mice were euthanized at day 30 post-stroke and the brains were collected for assessment of inflammation, white matter injury, tissue loss, and angiogenesis. Flow cytometry was performed on days 3 and 7 post-stroke to quantify infiltrated monocytes and neutrophils and CXCL12/CXCR4 signaling. Results Brain CD13 expression and infiltrated CD13+ monocytes and neutrophils increased acutely after the stroke. The brain CD13+lectin+ blood vessels increased on day 15 after the stroke. Similarly, an increase in the percentage area CD13 was observed in human stroke patients at the subacute time after stroke. Deletion of CD13 resulted in reduced infarct volume and improved neurological recovery after acute stroke. However, CD13KO mice had significantly worse memory deficits, amplified gliosis, and white matter damage compared to wild-type animals at chronic time points. CD13-deficient mice had an increased percentage of CXCL12+cells but a reduced percentage of CXCR4+cells and decreased angiogenesis at day 30 post-stroke. Conclusions CD13 is involved in the trans-migration of monocytes and neutrophils after stroke, and acutely, led to decreased infarct size and improved behavioral outcomes. However, loss of CD13 led to reductions in post-stroke angiogenesis by reducing CXCL12/CXCR4 signaling.

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“…A rigid and semiflexible docking process was deployed to remove the crystal water molecules, causing the fixed water molecules to possibly affect the conformation of the receptor-ligand complex. [ 21 , 22 ] Hydrogen atoms were added to the protein after completed the above procedure. To confirm the reliability of the combination mode, the initial inhibitor compound 10058-F4 was obtained from the binding site and then redocked into the crystal structure of c-Myc to compare the root-mean-square deviation (RMSD) between the 2 conformations.…”

Section: Methodsmentioning

confidence: 99%

Computational study on natural compounds inhibitor of c-Myc

Ren

Huangfu

et al. 2020

Medicine

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To screen and identify ideal leading compounds from a drug library (ZINC15 database) with potential inhibition effect against c-Myc to contribute to medication design and development. A series of computer-aided virtual screening techniques were performed to identify potential inhibitors of c-Myc. LibDock from the software Discovery Studio was used to do a structure-based screening after ADME (absorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was utilized to show the binding affinity and potential mechanism between ligands and c-Myc. Stability of the ligand-receptor complex was analyzed by molecular dynamic simulation at the end of the research. Compounds with more interactive energy which are confirmed to be the potential inhibitors for c-Myc were identified from the ZINC15 databases. Additionally, those compounds are also anticipated with fewer ames mutagenicity, rodent carcinogenicity, nondevelopmental toxic potential, and tolerant with cytochrome p450 2D6(CYP2D6). Dynamic simulation analysis also revealed that the very compounds had more favorable potential energy compared with 10058-F4(ZINC12406714). Furthermore, we prove that those compounds are stable and can exist in natural conditions. This study demonstrates that the compounds are potential therapeutic inhibitors for c-Myc. These compounds are safe and stable for drug candidates and may play a critical role in c-Myc inhibitor development.

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Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human Sinusoidal Endothelium Is Associated with Decreased Expression of CD13

Cited by 10 publications

References 49 publications

MDSCs: Key Criminals of Tumor Pre-metastatic Niche Formation

MDSCs: Key Criminals of Tumor Pre-metastatic Niche Formation

CD13 facilitates immune cell migration and aggravates acute injury but promotes chronic post-stroke recovery

Computational study on natural compounds inhibitor of c-Myc

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