Immature dendritic cell-derived exosomes rescue septic animals via milk fat globule epidermal growth factor VIII

Miksa, Michael; Wu, Rongqian; Dong, Wang-chao; Komura, Hidefumi; Amin, Dhara N.; Ji, You; Wang, Z.; Wang, H.; Ravikumar, T. S.; Tracey, Kevin J.; Wang, P.

doi:10.4049/jimmunol.0990106

Cited by 23 publications

(36 citation statements)

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“…However, the exact mechanism is unknown. We have previously demonstrated beneficial effects using rmMFG-E8 as a treatment at various time points in sepsis and other models of organ injuries [17,34,35]. For instance, rats treated with two bolus infusions of rmMFG-E8 (5 and 10 h after CLP) showed significant decreases in TNF-a and HMGB-1 [17].…”

Section: Discussionmentioning

confidence: 99%

“…The structure and sequence of the human MFG-E8 (hMFG-E8) is similar to mMFG-E8, except for a single EGF-like domain and the lack of a proline/threonine-rich domain in hMFG-E8. Our recent studies have shown that MFG-E8 is downregulated in septic mice [15] and that a deficiency in MFG-E8 is harmful in sepsis [17]. Investigators MFG-E8 exerts its effects, looking at the MAPK and NF-jB signaling pathways [28], CD14 or TLR4 [15], fractalkine [29], Akt [29][30][31][32], and osteopontin (OPN) [33].…”

Section: Discussionmentioning

confidence: 99%

“…Animal model of cecal ligation and puncture (CLP) Polymicrobial sepsis was induced by CLP as previously described [17]. Animals were euthanized 20 h after CLP.…”

Section: Experimental Animalsmentioning

confidence: 99%

“…Vehicle-treated animals received 160 lg/kg BW of human albumin. We formulated concentrations based on our previous knowledge [17].…”

Section: Administration Of Rhmfg-e8mentioning

confidence: 99%

“…We have previously shown that the administration of recombinant murine MFG-E8 (rmMFG-E8) provides many beneficial effects, including attenuating the proinflammatory response during sepsis, increasing apoptotic cell clearance, and lessening acute lung injury in an animal model of intestinal ischemia-reperfusion injury [15][16][17]. In our previous studies, we used a single dose of rmMFG-E8.…”

Section: Introductionmentioning

confidence: 99%

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Recombinant human milk fat globule-EGF factor 8 produces dose-dependent benefits in sepsis

Shah

Jacob

et al. 2011

Intensive Care Med

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Animal model of cecal ligation and puncture (CLP) Polymicrobial sepsis was induced by CLP as previously described [17]. Animals were euthanized 20 h after CLP.…”

Section: Experimental Animalsmentioning

confidence: 99%

“…Vehicle-treated animals received 160 lg/kg BW of human albumin. We formulated concentrations based on our previous knowledge [17].…”

Section: Administration Of Rhmfg-e8mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recombinant human milk fat globule-EGF factor 8 produces dose-dependent benefits in sepsis

Shah

Jacob

et al. 2011

Intensive Care Med

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Flow cytometric analysis of circulating microparticles in plasma

2010

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Microparticles, which include exosomes, micro-vesicles, apoptotic bodies and apoptotic microparticles, are small (0.05 -3 lm in diameter), membranous vesicles that can contain DNA, RNA, miRNA, intracellular proteins and express extracellular surface markers from the parental cells. They can be secreted from intracellular multivesicular bodies or released from the surface of blebbing membranes. Circulating microparticles are abundant in the plasma of normal individuals and can be derived from circulating blood cells such as platelets, red blood cells and leukocytes as well as from tissue sources, such as endothelial and placental tissues. Elevated levels of microparticles are associated with various diseases such as thrombosis (platelet microparticles), congestive heart failure (endothelial microparticles), breast cancer patients (leukocyte microparticles) and women with preeclampsia (syncytiotrophoblast microparticles). Although microparticles can be detected by microscopy, enzyme-linked immunoassays and functional assays, flow cytometry is the preferred method because of the ability to quantitate (fluorescent bead-or flow rate-based method) and because of polychromatic capabilities. However, standardization of pre-analytical and analytical modus operandi for isolating, enumerating and fluorescent labeling of microparticles remains a challenge. The primary focus of this article is to review the preliminary steps required to optimally study circulating in vivo microparticles which include: 1) centrifugation speed used, 2) quantitation of microparticles before antibody labeling, 3) levels of fluorescence intensity of antibody-labeled microparticles, 4) polychromatic flow cytometric analysis of microparticle sub-populations and 5) use of polyclonal antibodies designed for Western blotting for flow cytometry. These studies determine a roadmap to develop microparticles as biomarkers for a variety of conditions. ' 2010 International Society for Advancement of Cytometry Key terms quantitation of plasma microparticles; polychromatic flow cytometric analysis; Western blotting polyclonal antibodies OVER the years, the quiet waters of flow cytometric analysis of circulating microparticles (MPs) have given way to a deluge of original articles, technical briefs, and critical reviews. However, given the vast scope of work about circulating MPs, it is not possible to cover all the literature. Instead, this review focuses on flow cytometric analysis and applications of fetal-derived MPs. Although other cell-derived MPs such as platelet MPs (PMPs), endothelial MPs (EMPs), and leukocyte MP (LMPs) are not a focus of this review, many of the same principles apply.

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Milk Fat Globule–Epidermal Growth Factor–Factor 8 Improves Hepatic Steatosis and Inflammation

et al. 2020

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Background and Aims Milk fat globule–epidermal growth factor–factor 8 (MFGE8) has been shown to be a critical extracellular molecule that mediates apoptotic signaling in the pathological process of nonalcoholic fatty liver disease (NAFLD). MFGE8 is abundantly expressed in hepatocytes, but its function in the pathogenesis of NAFLD has not been characterized. Approach and Results In our current study, hepatic MFGE8 showed a protective role in the pathogenesis of NAFLD. Hepatic MFGE8 deletion largely exacerbated lipid accumulation and inflammatory responses in the liver in response to overnutrition. Mechanistically, intercellular MFGE8 was shown to directly bind to apoptosis signal‐regulating kinase 1 (ASK1) and to inhibit its dimerization and phosphorylation under a normal diet. However, under metabolic challenges, decreased cytoplasmic MFGE8 facilitated the dimerization and phosphorylation of ASK1 and subsequent mitogen‐activated protein kinase signaling in hepatocytes. Conclusions Hepatic MFGE8 is an endogenous inhibitor that halts the progression of hepatic steatosis and inflammation. Metabolic challenge–induced loss of intracellular MFGE8 facilitates ASK1 dimerization and phosphorylation. Therefore, maintaining hepatic MFGE8 levels may serve as an alternative strategy for the treatment of NAFLD.

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Immature dendritic cell-derived exosomes rescue septic animals via milk fat globule epidermal growth factor VIII

Cited by 23 publications

References 0 publications

Recombinant human milk fat globule-EGF factor 8 produces dose-dependent benefits in sepsis

Recombinant human milk fat globule-EGF factor 8 produces dose-dependent benefits in sepsis

Flow cytometric analysis of circulating microparticles in plasma

Milk Fat Globule–Epidermal Growth Factor–Factor 8 Improves Hepatic Steatosis and Inflammation

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