Organization and functions of glycolipid-enriched microdomains in phagocytes

• Lactosylceramide is highly expressed on neutrophil plasma membrane.
• Lactosylceramide acts as PPR, and an inducer of chemotaxis and superoxide anions.
• C24-lactosylceramide is connected with Src family kinase Lyn.
• PtdGlc forms distinct lipid domains on the outer leaflet of plasma membrane.
• Anti-PtdGlc antibody DIM21 can induce the apoptosis cascade in neutrophils.

Populations of glycolipids change markedly during leukocyte differentiation, suggesting that these molecules are involved in biological functions. About 70% of the glycosphingolipids in human neutrophils are lactosylceramide, a molecule also expressed on monocytes and dendritic cells, but not on lymphocytes. In contrast, phosphatidylglucoside is mainly expressed on neutrophils. STED microscopic analysis showed that phosphatidylglucoside and lactosylceramide form different domains on plasma membranes of neutrophils, with phosphatidylglucoside preferentially expressed along the neutrophil differentiation pathway. Phosphatidylglucoside was found to mediate the differentiation of HL-60 cells into the neutrophilic lineage, and to be involved in FAS-dependent neutrophil apoptosis. In contrast, lactosylceramide was only expressed on mature neutrophils. Complexes of lactosylceramide and the Src family kinase Lyn form membrane microdomains. LacCer-enriched membrane microdomains mediate neutrophil innate immune responses; e.g. chemotaxis, phagocytosis, and superoxide generation. C24 fatty acid chains of LacCer are indispensable for the formation of LacCer–Lyn complexes and for LacCer-dependent functions. Moreover, Lyn-coupled LacCer-enriched microdomains serve as signal transduction platforms for αMβ2 integrin-mediated phagocytosis. This review describes the organization and potential functions of glycolipids in phagocytes, as well as the roles of both phosphatidylglucoside and lactosylceramide in neutrophils. This article is part of a Special Issue entitled Linking transcription to physiology in lipidomics.