Macrophage reprogramming by negatively charged membrane phospholipids controls infection

Abstract

Extracellular vesicles (ECVs) are heterogeneous membrane‐enclosed structures containing proteins, nucleic acids, and lipids that participate in intercellular communication by transferring their contents to recipient cells. Although most of the attention has been directed at the biologic effect of proteins and microRNA, the contribution of phospholipids present in ECVs on cellular activation has not been extensively addressed. We investigated the biologic effect of phosphatidylserine (PS) and phosphatidylcholine (PC), 2 phospholipids highly abundant in ECVs. A transcriptomic analysis revealed that ∼4700 genes were specifically modified by exposing peritoneal macrophages to PS or PC liposomes in vivo. Among them, the expression of several chemokines and cytokines was highly upregulated by PS liposome treatment, translating into a massive neutrophil infiltration of the peritoneum capable of neutralizing a septic polymicrobial insult. Both the l and d stereoisomers of PS induced the same response, suggesting that the effect was related to the negative charge of the phospholipid head. We concluded that an increase in the internal negative charge of the cell triggers a signaling cascade activating an innate immune response capable of controlling infection.—Cauvi, D. M., Hawisher, D., Dores‐Silva, P. R., Lizardo, R. E., De, Maio, A. Macrophage reprogramming by negatively charged membrane phospholipids controls infection. FASEB J. 33, 2995–3009 (2019). http://www.fasebj.org

Early hyperbaric oxygen therapy improves survival in a model of severe sepsis

“…The early protective effect of HBOT echoes a prior study defining the therapeutic window for sepsis resolution in this model of CLP within Ͻ6 h of the insult (13). In addition, a robust presence of neutrophils within the peritoneum before CLP reduced the bacterial load substantially and improved mouse survival, demonstrating that early source control is critical for sepsis resolution (12). Therefore, we have hypothesized that early events at the immunological and metabolic level are responsible for determining the final outcome of sepsis.…”

Liposomes used as a vaccine adjuvant-delivery system: From basics to clinical immunization

“…Also, Cauvi et al revealed in murine model that anionic empty PS liposomes triggered peritoneal MPs to have about 4700 genes specifically modified, resulting in changed protein expressions by peritoneal cells, including increased secretion of several chemokines (CXCL1, CXCL2, CSF-2, and CSF-3) and cytokines (TNF-a, IL-6, IL-10). And consequently, massive neutrophil infiltration into the peritoneum succeeded and proved capable of neutralizing a septic polymicrobial insult [98]. However, such neutralization of pathogens was also obtained by intraperitoneal administration of PG liposomes, suggesting that these effects might be just caused by the negative charge property of phospholipids, through possibly increasing the absolute value of the negative potential of MP plasma internal membranes.…”

Beyond Trial and Error: A Systematic Development of Liposomes Targeting Primary Macrophages

“…Although these results suggest that the fluidity of the acyl chain contributes to particle uptake, a direct correlation between those two parameters was not possible: despite the fact that POPC liposomes have a lower anisotropy than the DOPC/DSPC mixture, the latter formulation was taken up to a higher extent. POPC/POPS‐based liposomes which modulate various cellular signaling pathways have been already used to reprogram macrophages, [ 36 ] and POPC is responsible for the activation of alveolar macrophages and regulating their production of cytokines. [ 37 ] However, the liposomal effect was attributed mainly to the presence of PS, whereas a comparison with other PC‐based liposomes and the lipid chain contribution on the uptake has so far been completely missing.…”