[Frontiers in Bioscience, Landmark, 20, 325-334, January 1, 2015]

Involvement of glycosphingolipid-enriched lipid rafts in inflammatory responses

Kazuhisa Iwabuchi 1

1Infectious Control Nursing, Graduate School of Health Care and Nursing; Institute for Environmental and Gender-specific Medicine, Graduate School of Medicine, Juntendo University, Chiba, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. What are GSL-enriched lipid rafts?
4. Lactosylceramide is a key player in the human innate immunosystem
5. Lactosylceramide-enriched lipid rafts mediate superoxide generation
6. Lactosylceramide-enriched lipid rafts mediate inflammation
7 Conclusion
8. Acknowledgment
9. References

1. ABSTRACT

Glycosphingolipids (GSLs) are membrane components consisting of hydrophobic ceramide and hydrophilic sugar moieties. GSLs cluster with cholesterol in cell membranes to form GSL-enriched lipid rafts. Biochemical analyses have demonstrated that GSL-enriched lipid rafts contain several kinds of transducer molecules, including Src family kinases. Among the GSLs, lactosylceramide (LacCer, CDw17) can bind to various microorganisms, is highly expressed on the plasma membranes of human phagocytes, and forms lipid rafts containing the Src family tyrosine kinase Lyn. LacCer-enriched lipid rafts mediate immunological and inflammatory reactions, including superoxide generation, chemotaxis, and non-opsonic phagocytosis. Therefore, LacCer-enriched membrane microdomains are thought to function as pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) expressed on microorganisms. LacCer also serves as a signal transduction molecule for functions mediated by CD11b/CD18-integrin (αM/β2-integrin, CR3, Mac-1), as well as being associated with several key cellular processes. LacCer recruits PCKα/ε and phospholipase A2 to stimulate PECAM-1 expression in human monocytes and their adhesion to endothelial cells, as well as regulating β1-integrin clustering and endocytosis on cell surfaces. This review describes the organizational and inflammation-related functions of LacCer-enriched lipid rafts.

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Key Words: Glycosphingolipid, Lactosylceramide, Lipid Rafts, Superoxide Generation, Inflammation, Innate Immunity, Review

Send correspondence to: Kazuhisa Iwabuchi, Infectious Control Nursing, Graduate School of Health Care and Nursing, Juntendo University, 2-5-1 Takasu, Urayasu-shi, Chiba 279-0023, Japan, Tel: 81-47-353-3171, Fax: 81-47-353-3178, E-mail: iwabuchi@med.juntendo.ac.jp