Biology: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
- ↑ CDw17+antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 "Convergence: Lactosylceramide-Centric Signaling Pathways Induce Inflammation, Oxidative Stress, and Other Phenotypic Outcomes". International Journal of Molecular Sciences 22 (4): 1816. February 2021. doi:10.3390/ijms22041816. PMID 33673027.
- ↑ "CDw17". The Leucocyte Antigen Factsbook. Factsbook Series (2nd ed.). San Diego: Academic Press. 1997. p. 176. doi:10.1016/B978-012078185-0/50452-2. ISBN 978-0-12-078185-0.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Ekyalongo, Roudy C.; Nakayama, Hitoshi; Kina, Katsunari; Kaga, Naoko; Iwabuchi, Kazuhisa (2014-06-23). "Organization and functions of glycolipid-enriched microdomains in phagocytes" (in en). 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. https://linkinghub.elsevier.com/retrieve/pii/S1388198114001206.
- ↑ 5.0 5.1 Dong, Liang; Cao, Zhi; Han, Weidong; Wu, Zhiqiang (2025-09-29). "Synthesis, function, and therapeutic potential of glycosphingolipids" (in English). Frontiers in Immunology 16. doi:10.3389/fimmu.2025.1673713. ISSN 1664-3224. PMID 41089704.
- ↑ 6.0 6.1 6.2 6.3 Nakayama, Hitoshi; Iwahara, Chihiro; Takamori, Kenji; Ogawa, Hideoki; Iwabuchi, Kazuhisa (2008-12-01). "Lactosylceramide is a Pattern Recognition Receptor that Forms Lyn-Coupled Membrane Microdomains on Neutrophils" (in en). Immunology' Endocrine & Metabolic Agents in Medicinal Chemistry 8 (4): 327–335. doi:10.2174/187152208787169251. http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1871-5222&volume=8&issue=4&spage=327.
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 Iwabuchi, Kazuhisa; Nakayama, Hitoshi; Hanafusa, Kei (2022-04-04). "Lactosylceramide-enriched microdomains mediate human neutrophil immunological functions via carbohydrate-carbohydrate interaction" (in en). Glycoconjugate Journal 39 (2): 239–246. doi:10.1007/s10719-022-10060-0. ISSN 0282-0080. PMID 35377103. https://link.springer.com/10.1007/s10719-022-10060-0.
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