The regulatory roles of glycosphingolipid‐enriched lipid rafts in immune systems

Nakayama, Hitoshi; Nagafuku, Masakazu; Suzuki, Akemi; Iwabuchi, Kazuhisa; Inokuchi, Jin-ichi

doi:10.1002/1873-3468.13275

Cited by 59 publications

(62 citation statements)

References 175 publications

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“…GSLs at the cell surface also play direct roles in adhesion/recognition processes. For example, specific GSLs are involved in binding of pathogenic viruses, microorganisms, and bacterial toxins [32,33]. The topic was recently reviewed [34].…”

Section: Glucosylceramide As Intermediate Of Glycosphingolipidsmentioning

confidence: 99%

Glucocerebrosidase: Functions in and Beyond the Lysosome

Boer

Smeden

Bouwstra

et al. 2020

JCM

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Glucocerebrosidase (GCase) is a retaining β-glucosidase with acid pH optimum metabolizing the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose. Inherited deficiency of GCase causes the lysosomal storage disorder named Gaucher disease (GD). In GCase-deficient GD patients the accumulation of GlcCer in lysosomes of tissue macrophages is prominent. Based on the above, the key function of GCase as lysosomal hydrolase is well recognized, however it has become apparent that GCase fulfills in the human body at least one other key function beyond lysosomes. Crucially, GCase generates ceramides from GlcCer molecules in the outer part of the skin, a process essential for optimal skin barrier property and survival. This review covers the functions of GCase in and beyond lysosomes and also pays attention to the increasing insight in hitherto unexpected catalytic versatility of the enzyme.

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Section: Glucosylceramide As Intermediate Of Glycosphingolipidsmentioning

confidence: 99%

Glucocerebrosidase: Functions in and Beyond the Lysosome

Boer

Smeden

Bouwstra

et al. 2020

JCM

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“…These results indicate that SHIP-1 is essential for resistance to bacterial infection. Lipid rafts play important roles in innate and adaptive immunity by recruiting cellular signaling modifiers for T-cell activation, phagocytosis, and so on (48). The integrity of lipid rafts is implicated to be essential for LPS cellular activation owing to the presence of CD14, chemokine receptor 4, and tolllike receptor 4 on lipid microdomains of cell membrane following LPS stimulation (49).…”

Section: Discussionmentioning

confidence: 99%

SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection

Qin

Zhou

et al. 2020

Front. Immunol.

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SHIP-1 is an inositol phosphatase that hydrolyzes phosphatidylinositol 3-kinase (PI3K) products and negatively regulates protein kinase B (Akt) activity, thereby modulating a variety of cellular processes in mammals. However, the role of SHIP-1 in bacterial-induced sepsis is largely unknown. Here, we show that SHIP-1 regulates inflammatory responses during Gram-negative bacterium Pseudomonas aeruginosa infection. We found that infected-SHIP-1 −/− mice exhibited decreased survival rates, increased inflammatory responses, and susceptibility owing to elevated expression of PI3K than wild-type (WT) mice. Inhibiting SHIP-1 via siRNA silencing resulted in lipid raft aggregates, aggravated oxidative damage, and bacterial burden in macrophages after PAO1 infection. Mechanistically, SHIP-1 deficiency augmented phosphorylation of PI3K and nuclear transcription of signal transducer and activator of transcription 5 (STAT5) to induce the expression of Trib1, which is critical for differentiation of M2 but not M1 macrophages. These findings reveal a previously unrecognized role of SHIP-1 in inflammatory responses and macrophage homeostasis during P. aeruginosa infection through a PI3K/Akt-STAT5-Trib1 axis.

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“…These lipids are abundant components of the cell membrane [ 27 ]. GSLs are related to many biological processes including infections by specific pathogens as binding receptors at the surface of host cells [ 28 ]. GSLs play a role in immune cell function as a signal transducer (i.e., toxins or IgM antibodies) or in binding lipid rafts to trigger chemotaxis, phagocytosis and phagolysosome formation [ 28 ] and are involved in regulatory aspects of T cell biology [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Potential Lipid Signatures for Diagnosis and Prognosis of Sepsis and Systemic Inflammatory Response Syndrome

et al. 2020

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Systemic inflammatory response syndrome (SIRS) and sepsis are two conditions which are difficult to differentiate clinically and which are strongly impacted for prompt intervention. This study identified potential lipid signatures that are able to differentiate SIRS from sepsis and to predict prognosis. Forty-two patients, including 21 patients with sepsis and 21 patients with SIRS, were involved in the study. Liquid chromatography coupled to mass spectrometry and multivariate statistical methods were used to determine lipids present in patient plasma. The obtained lipid signatures revealed 355 features for the negative ion mode and 297 for the positive ion mode, which were relevant for differential diagnosis of sepsis and SIRS. These lipids were also tested as prognosis predictors. Lastly, L-octanoylcarnitine was found to be the most promising lipid signature for both the diagnosis and prognosis of critically ill patients, with accuracies of 75% for both purposes. In short, we presented the determination of lipid signatures as a potential tool for differential diagnosis of sepsis and SIRS and prognosis of these patients.

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The regulatory roles of glycosphingolipid‐enriched lipid rafts in immune systems

Cited by 59 publications

References 175 publications

Glucocerebrosidase: Functions in and Beyond the Lysosome

Glucocerebrosidase: Functions in and Beyond the Lysosome

SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection

Potential Lipid Signatures for Diagnosis and Prognosis of Sepsis and Systemic Inflammatory Response Syndrome

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