CDw17 antigen

The CDw17 antigen, also known as CD17 or lactosylceramide[1] (LacCer), is a glycosphingolipid found in microdomains on the plasma membrane of numerous cells.[2] It has been reported on human neutrophils, basophils, monocytes, platelets, tonsillar CD45+ dendritic cells, epithelial cells, endothelial cells in intestinal epithelium, and on post-proliferative granulocytes in the bone marrow. [2][3]

CDw17/LacCer acts as a precursor for the biosynthesis of an extensive array of glycosphingolipids[2] and as a bioactive lipid involved in cell signaling.[2] It is associated with particular types of lipid rafts, also called glycolipid-enriched membrane microdomains, where it can help organize signaling molecules involved in inflammation and immune-cell responses pathways on the cell surface and connecting them to internal cellular response cascades; in human neutrophils, LacCer-enriched microdomains have been linked to chemotaxis, phagocytosis, and superoxide generation.[4]

Function

Lactosylceramide is synthesized from glucosylceramide by lactosylceramide synthase, which transfers galactose from UDP-galactose to glucosylceramide.[2] LacCer can then act as a precursor for more complex glycosphingolipids, like globosides, sulfatides, gangliosides, and other neutral glycosphingolipids.[2]

LacCer also acts as a branch point for many major glycosphingolipid classes, including the globo, lacto, ganglio, and asialo series of glycosphingolipids.[5] One example is the enzyme A4GALT aiding the transfer of galactose to lactosylceramide to form globotriaosylceramide.[5]

Beyond its role as a precursor, LacCer has been described as a bioactive lipid.[2] It has been associated with signaling pathways related to cell adhesion, cell migration, inflammation, angiogenesis, oxidative stress, and cell proliferation.[2] Because it is enriched in glycolipid membrane microdomains, LacCer may help concentrate signaling molecules at the cell surface and transmit extracellular signals into the cell.[2][4]

Role in Phagocytes

LacCer has been studied in phagocytes, especially human neutrophils, where it is highly expressed on the plasma membrane and forms glycolipid-enriched microdomains.[4] These microdomains are associated with signaling proteins such as Lyn, a Src-family kinase.[4][6]

LacCer-enriched microdomains have been shown to be involved in many neutrophil immune functions, like chemotaxis, phagocytosis, and superoxide generation.[4][6] Beyond its capacity as a structural membrane lipid, it also functions as part of a signaling platform that helps neutrophils respond to microbial or pathogenic stimuli.[6][7]

The fatty acid chain composition of LacCer may affect this signaling role.[7] Long chain C24 LacCer species have been reported to support the association of LacCer-enriched microdomains with Lyn, helping connect recognition at the cell surface to intracellular responses involved in neutrophil migration and phagocytosis.[4][7]

Interaction with Microorganisms

LacCer-enriched microdomains may participate in innate immune recognition by binding pathogen-associated molecules.[6][7] The carbohydrate part of LacCer can interact with carbohydrate structures on microorganisms, including fungal β-glucans and mycobacterial lipoarabinomannan.[7] These carbohydrate-carbohydrate interactions can help trigger intracellular signaling pathways involved in neutrophil movement, engulfment, and production of reactive oxygen species.[7]

In human neutrophils, LacCer has been reported to bind pathogen-specific molecules such as Candida albicans-derived β-glucans and mycobacterial lipoarabinomannan.[7] Studies of mycobacteria suggest that LacCer on neutrophils can interact with mannose-capped lipoarabinomannan on the bacterial surface during phagocytosis.[7]

Inflammation and Oxidative Stress

LacCer has also been linked to inflammatory and oxidative stress pathways.[2] Several inflammatory or growth-related stimuli, including tumor necrosis factor α, oxidized low-density lipoprotein, platelet-derived growth factor, vascular endothelial growth factor, stress, cigarette smoke, and nicotine, have been reported to increase LacCer synthesis or LacCer-centered signaling.[2]

Newly synthesized LacCer can activate NADPH oxidase, contributing to reactive oxygen species production.[2] LacCer can also activate cytosolic phospholipase A2, which releases arachidonic acid for downstream inflammatory lipid pathways.[2] These pathways have been discussed in relation to inflammation, oxidative stress, cell adhesion, angiogenesis, and other disease.[2]

References

  1. ↑ CDw17+antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Chatterjee S, Balram A, Li W (February 2021). "Convergence: Lactosylceramide-Centric Signaling Pathways Induce Inflammation, Oxidative Stress, and Other Phenotypic Outcomes". International Journal of Molecular Sciences. 22 (4): 1816. doi:10.3390/ijms22041816. PMC 7917694. PMID 33673027.
  3. ↑ Barclay AN, Brown MH, Law SK, McKnight AJ, Tomlinson MG, van der Merwe PA (1997). "CDw17". In Barclay AN (ed.). The Leucocyte Antigen Factsbook. Factsbook Series (2nd ed.). San Diego: Academic Press. p. 176. doi:10.1016/B978-012078185-0/50452-2. ISBN 978-0-12-078185-0.
  4. 1 2 3 4 5 6 Ekyalongo RC, Nakayama H, Kina K, Kaga N, Iwabuchi K (2014-06-23). "Organization and functions of glycolipid-enriched microdomains in phagocytes". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1851 (1): 90–97. doi:10.1016/j.bbalip.2014.06.009. PMID 24968752.
  5. 1 2 Dong L, Cao Z, Han W, Wu Z (2025-09-29). "Synthesis, function, and therapeutic potential of glycosphingolipids". Frontiers in Immunology. 16 1673713. doi:10.3389/fimmu.2025.1673713. ISSN 1664-3224. PMC 12515973. PMID 41089704.
  6. 1 2 3 4 Nakayama H, Iwahara C, Takamori K, Ogawa H, Iwabuchi K (2008-12-01). "Lactosylceramide is a Pattern Recognition Receptor that Forms Lyn-Coupled Membrane Microdomains on Neutrophils". Immunology' Endocrine & Metabolic Agents in Medicinal Chemistry. 8 (4): 327–335. doi:10.2174/187152208787169251.
  7. 1 2 3 4 5 6 7 8 Iwabuchi K, Nakayama H, Hanafusa K (2022-04-04). "Lactosylceramide-enriched microdomains mediate human neutrophil immunological functions via carbohydrate-carbohydrate interaction". Glycoconjugate Journal. 39 (2): 239–246. doi:10.1007/s10719-022-10060-0. ISSN 0282-0080. PMID 35377103.
This page is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.