In our physiologic mouse model of chronic E-cigarette exposure and sepsis, E-cigarette vapor inhalation led to reduced neutrophil migration into infected spaces and a higher burden of Pseudomonas.
These data provide new insights into the molecular basis of M1 and M2 phenotypic dichotomy and identify gp130 as a key regulator of immune homeostasis during sepsis.
Our results indicate that Gal-3, secreted during sepsis, inhibits neutrophil migration into the infectious focus, which promotes the bacterial spread and worsens the outcome of sepsis.
RX-207 reduced neutrophil migration in thioglycollate-induced peritonitis (37%), inhibited carrageenan-induced paw edema (32%) and cerulein-induced pancreatitis (28%), and increased animal survival in the mouse model of cecal ligation and puncture (CLP)-induced sepsis (60%).
We sought to determine the role of trimetazidine (TMZ) in regulation of neutrophil migration to the heart in a mouse model of sepsis and endotoxemia, and to identify the mechanism whereby TMZ confers a survival advantage.
Neutrophil receptors play key roles in chemotactic neutrophil migration and may prove to be suitable targets in future pharmacological therapies for sepsis.
Here we demonstrate that Cl-amidine treatment prior to CLP improves overall survival in sepsis and the abrogation of PAD4 has minimal effects on the proinflammatory immune response to sepsis, while it has no effect on overall neutrophil migration to the peritoneum.
Excessive ADAM17 sheddase activity during sepsis thus appears to undermine in a direct and indirect manner the necessary balance between intravascular adhesion and de-adhesion events that regulate neutrophil migration into sites of infection.
Taken together, our results demonstrate that Wip1 can negatively regulate neutrophil migration and antimicrobial immunity during sepsis and inhibition of Wip1 can be a potential therapeutic target for sepsis treatment.
Although β2 integrins have been shown to mediate neutrophil transendothelial migration during systemic and local inflammation, relatively little information is available regarding neutrophil migration in sepsis beyond the endothelial cell layer.
These results put in evidence a striking protective role of Ang-2 in experimental sepsis evoked by a multidrug-resistant isolate of P. aeruginosa attributed to modulation of TNF-α production and changes in neutrophil migration.
This downregulation increases neutrophil migration to the site of infection, preventing bacterial spread and development of a fulminant lethal systemic infection.