Exosomes, not protein or lipids, in mesenteric lymph activate inflammation

Kojima, Mitsuaki; Gimenes-Júnior, João Antonio; Langness, Simone; Lavoie-Gagne, Ophelie; Eliceiri, Brian P.; Costantini, Todd W.; Coimbra, Raúl

doi:10.1097/ta.0000000000001296

Cited by 34 publications

(33 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even though many studies have focused on exosomes' role in cancer, their role in injury or hemorrhagic shock remains unknown. Recently, our group showed the relevance of ML exosomes in inflammatory response after injury by identifying the presence of exosomes in rat ML and showing that they have the ability to induce inflammatory responses in monocytes in vitro (14). To extend our previous findings to an in vivo context, we studied the effect of injection of ML exosomes on lung injury in naive mice.…”

Section: Discussionmentioning

confidence: 95%

“…2). Purified exosomes from ML were characterized by electron microscopy and immunoblotting (CD63 and heat shock protein 70) in our previous study (14).…”

Section: Animalsmentioning

confidence: 99%

“…Exosomes carry a variety of biologically active contents, including lipids, protein, mRNAs, and micro-RNAs, all of which may have inflammatory and immunomodulatory effects on target cells (13). We have recently identified the presence of exosomes in rat ML and demonstrated that exosomes in postshock ML have the ability to trigger NF-kB activation and proinflammatory cytokine production in monocytes and macrophages in vitro (14). Interestingly, recent studies have demonstrated that exosomes isolated from tumor cell lines as well as several body fluids (i.e., serum, amniotic fluid, liver cirrhosis ascites, and malignant ascites) induce proinflammatory cytokine production in monocytes and macrophages via TLR-dependent signaling pathways (15)(16)(17).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

et al. 2017

Self Cite

View full text Add to dashboard Cite

Acute lung injury (ALI) is a common cause of morbidity in patients after severe injury due to dysregulated inflammation, which is believed to be driven by gut-derived inflammatory mediators carried mesenteric lymph (ML). We have previously demonstrated that nano-sized extracellular vesicles, called exosomes, secreted into ML after trauma/hemorrhagic shock (T/HS) have the potential to activate immune cells Here, we assess the function of ML exosomes in the development of T/HS-induced ALI and the role of TLR4 in the ML exosome-mediated inflammatory response. ML exosomes isolated from rats subjected to T/HS stimulated NF-κB activation and caused proinflammatory cytokine production in alveolar macrophages. experiments revealed that intravenous injection of exosomes harvested after T/HS, but not before shock, caused recruitment of inflammatory cells in the lung, increased vascular permeability, and induced histologic ALI in naive mice. The exosome-depleted supernatant of ML had no effect on and inflammatory responses. We also demonstrated that both pharmacologic inhibition and genetic knockout of TLR4 completely abolished ML exosome-induced cytokine production in macrophages. Thus, our findings define the critical role of exosomes secreted into ML as a critical mediator of T/HS-induced ALI through macrophage TLR4 activation.-Kojima, M., Gimenes-Junior, J. A., Chan, T. W., Eliceiri, B. P., Baird, A., Costantini, T. W., Coimbra, R. Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation Toll-like receptor 4.

show abstract

Section: Discussionmentioning

confidence: 95%

“…2). Purified exosomes from ML were characterized by electron microscopy and immunoblotting (CD63 and heat shock protein 70) in our previous study (14).…”

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…The effect of the trauma-induced ‘toxic lymph’ 167 and shift in the ratio of T H 17 cells to T reg cells can be counterbalanced by stimulation of the vagal nerve 172 . In particular, CD63 + HSP70 + exosomes within the mesenteric lymph nodes represent a major trigger for the monocyte-macrophage pro-inflammatory response 174 .…”

Section: Posttraumatic Immune Response and Breakdown Of Protective Cementioning

confidence: 99%

Innate immune responses to trauma

2018

View full text Add to dashboard Cite

Trauma can affect any individual at any location and at any time over a lifespan. The disruption of macrobarriers and microbarriers induces instant activation of innate immunity. The subsequent complex response, designed to limit further damage and induce healing, also represents a major driver of complications and fatal outcome after injury. This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier.

show abstract

“…Most cells can secrete exosomes under normal conditions, whereas under pathologic or stress conditions exosome quantity or content may be altered . Reports suggest that exosomes mediate intercellular communication, stimulate target cells, promote antigen presentation, transfer pathogens, and regulate immune responses …”

Section: Introductionmentioning

confidence: 99%

Frontline Science: Macrophage-derived exosomes promote neutrophil necroptosis following hemorrhagic shock

Jiao

Loughran

et al. 2017

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Hemorrhagic shock (HS) renders patients susceptible to development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) through mechanisms that are, as yet, unclear. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that controls cell release of inflammatory mediators from innate immune cells, such as polymorphonuclear neutrophils (PMNs), and critically regulates the progress of inflammation. In this study, we investigated the mechanisms of alveolar macrophage (AMϕ) effects on PMN necroptosis following HS. With the use of in vivo and ex vivo HS models, we reveal a novel function of shock-activated AMϕ in promoting PMN necroptosis. We demonstrate that exosomes released from HS-activated AMϕ induce mainly NADPH oxidase-derived reactive oxygen species (ROS) production inside PMNs and subsequent promotion of necroptosis. These findings explore a previously unidentified pathway of AMϕ-PMN cross-talk, which causes enhanced PMN necroptosis and subsequent exaggerated post-HS lung inflammation. The targeting of this PMN death pathway may serve as a new therapeutic strategy for treatment of post-HS SIRS.

show abstract

Exosomes, not protein or lipids, in mesenteric lymph activate inflammation

Abstract: Our findings show that exosomes, and not the liquid fraction of ML, are the major component triggering inflammatory responses in monocytes and macrophages after experimental T/HS.

Cited by 34 publications

References 37 publications

Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

Innate immune responses to trauma

Frontline Science: Macrophage-derived exosomes promote neutrophil necroptosis following hemorrhagic shock

Contact Info

Product

Resources

About