Macrophage activation status rather than repolarization is associated with enhanced checkpoint activity in combination with PI3Kg inhibition

2021 ◽  
pp. molcanther.0961.2020
Author(s):  
Larissa S. Carnevalli ◽  
Molly A. Taylor ◽  
Matthew King ◽  
Anna ML Coenen-Stass ◽  
Adina M Hughes ◽  
...  
Author(s):  
Foivos-Filippos Tsokanos ◽  
Carolin Muley ◽  
Sajjad Khani ◽  
Daniela Hass ◽  
Thomas Fleming ◽  
...  

AbstractMetabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated. However, a direct link between reactive metabolites and macrophage activation has not been demonstrated yet. Here, we show that acute MG treatment activated components of the p38 MAPK pathway and enhanced glycolysis in primary murine macrophages. MG induced a distinct gene expression profile sharing similarities with classically activated proinflammatory macrophages as well as metabolically activated macrophages usually found in obese patients. Transcriptomic analysis revealed a set of 15 surface markers specifically upregulated in MG-treated macrophages, thereby establishing a new set of targets for diagnostic or therapeutic purposes under high MG conditions, including diabetes. Overall, our study defines a new polarization state of macrophages that may specifically link aberrant macrophage activation to reactive metabolites in diabetes.


Reproduction ◽  
2000 ◽  
pp. 225-229 ◽  
Author(s):  
A Gul ◽  
C Kotan ◽  
I Dilek ◽  
T Gul ◽  
A Tas ◽  
...  

The aim of this study was to determine whether autologous erythrocyte suspension can be used as a dye for evaluation of tubal patency and whether it has any advantages over methylene blue or indigo carmine solutions. Reproductively healthy female nulliparous Wistar Albino rats (n = 30), aged 6 months, mass 165-195 g, were assigned randomly to three groups. Rats received a 1 ml i.p. injection of 5% (w/v) methylene blue solution (methylene blue group: n = 10), 5% (w/v) indigo carmine solution (indigo carmine group: n = 10) or 5% (v/v) fresh autologous erythrocyte suspension (autologous erythrocyte group: n = 10). At 4 weeks after injection, a small sterile opening was made in the peritoneal cavity of each rat. The cavity was rinsed once with TCM-199 to collect macrophages. The rinsed peritoneal contents were cultured overnight to evaluate macrophage activation. The peritoneal opening was expanded for evaluation of adhesion formation. Only one rat from the autologous erythrocyte group had intra-peritoneal adhesions (score 2), whereas all rats in the methylene blue group (score 1: n = 1; score 2: n = 4; score 3: n = 4; and score 4: n = 1) and seven rats in the indigo carmine group (score 1: n = 1; score 2: n = 2; score 3: n = 3; and score 4: n = 1) had intra-abdominal adhesions. Macrophage activity was observed in the cultured peritoneal contents collected from the methylene blue and indigo carmine groups but not from the autologous erythrocyte group. Adhesion formation could be due to macrophage activation caused by methylene blue and indigo carmine solutions. These results indicate that tubal patency can be observed by laparoscopy using autologous erythrocyte suspension. The results of this study are believed to be the first to indicate that a patient's own erythrocyte suspension could be used during observation of tubal patency by laparoscopy. However, further studies are required.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2012-P ◽  
Author(s):  
TETSUYA KUBOTA ◽  
MARIKO INOUE ◽  
NAOTO KUBOTA ◽  
ISEKI TAKAMOTO ◽  
KOHJIRO UEKI ◽  
...  

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