GSL-Enriched Membrane Microdomains in Innate Immune Responses
- PDF / 556,066 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 84 Downloads / 212 Views
REVIEW
GSL-Enriched Membrane Microdomains in Innate Immune Responses Hitoshi Nakayama • Hideoki Ogawa • Kenji Takamori • Kazuhisa Iwabuchi
Received: 10 July 2012 / Accepted: 13 February 2013 / Published online: 28 February 2013 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2013
Abstract Many pathogens target glycosphingolipids (GSLs), which, together with cholesterol, GPI-anchored proteins, and various signaling molecules, cluster on host cell membranes to form GSL-enriched membrane microdomains (lipid rafts). These GSL-enriched membrane microdomains may therefore be involved in host–pathogen interactions. Innate immune responses are triggered by the association of pathogens with phagocytes, such as neutrophils, macrophages and dendritic cells. Phagocytes express a diverse array of pattern-recognition receptors (PRRs), which sense invading microorganisms and trigger pathogen-specific signaling. PRRs can recognize highly conserved pathogen-associated molecular patterns expressed on microorganisms. The GSL lactosylceramide (LacCer, CDw17), which binds to various microorganisms, including Candida albicans, is expressed predominantly on the plasma membranes of human mature neutrophils and forms membrane microdomains together with the Src family tyrosine kinase Lyn. These LacCer-enriched membrane microdomains can mediate superoxide generation, migration, and phagocytosis, indicating that LacCer functions as a PRR in innate immunity. Moreover, the interactions of GSL-enriched membrane microdomains with membrane proteins, such as growth factor receptors, are important in mediating the physiological properties of these proteins. Similarly, we recently found that interactions between LacCer-enriched membrane microdomains H. Nakayama K. Iwabuchi Juntendo University Laboratory for Biochemistry, Faculty of Health Care and Nursing, Chiba, Japan H. Nakayama H. Ogawa K. Takamori K. Iwabuchi (&) Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan e-mail: [email protected]
and CD11b/CD18 (Mac-1, CR3, or aMb2-integrin) are significant for neutrophil phagocytosis of non-opsonized microorganisms. This review describes the functional role of LacCer-enriched membrane microdomains and their interactions with CD11b/CD18. Keywords Membrane microdomain Lactosylceramide Innate immunity Integrin Src family kinase
Introduction Glycosphingolipids (GSLs) are composed of hydrophobic ceramide and hydrophilic sugar moieties (Degroote et al. 2004). More than 400 types of GSL have been identified based on their sugar chain structures (Hakomori 2003). The ceramide structures of GSLs are also highly variable (Kaga et al. 2005). GSL metabolism and composition are specifically altered during the proliferation and differentiation of various cell types (Hakomori 2003; Sonnino et al. 2006), indicating that the expression patterns of GSLs may reflect the functions of these cells. The most important function of GSL, defining cell phe
Data Loading...
