ArticleThe Journal of allergy and clinical immunology2018
Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells.
Article in The Journal of allergy and clinical immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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Who cites it
41 citing papers in PubMed, 59 citations in OpenAlex.
- Selective elimination of mast cells via Siglec-6-targeted nanodelivery of drug payload.The Journal of allergy and clinical immunology · 2026Article
- Loss of erythrocyte sialic acid in sepsis disrupts inhibitory Siglec interactions, driving neutrophil hyperactivation and NET outspread.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Programmed Cell Death in Chronic Rhinosinusitis.Clinical and translational allergy · 2026Review
- Siglec-7 inhibits TLR3-induced pro-inflammatory cytokine production from human monocytes and macrophages.Frontiers in immunology · 2026Article
- Dysregulated Sialylation in Cancer: From Immunosuppressive Microenvironment to Siglec-Targeted Therapeutics.Biomolecules · 2025Review
- Eosinophil specialization is regulated by exposure to the esophageal epithelial microenvironment.Journal of leukocyte biology · 2024Article
- Article
- Flow cytometric immunophenotypic differentiation patterns of bone marrow eosinophilopoiesis.Cytometry. Part B, Clinical cytometry · 2024Article
- The Potential of Siglecs and Sialic Acids as Biomarkers and Therapeutic Targets in Tumor Immunotherapy.Cancers · 2024Review
- Tumor-Associated Macrophage Targeting of Nanomedicines in Cancer Therapy.Pharmaceutics · 2023Review
- Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases.Seminars in immunology · 2023Review
- Siglec-9 is an inhibitory receptor on human mast cells in vitro.The Journal of allergy and clinical immunology · 2023Article
- Airway transcriptome networks identify susceptibility to frequent asthma exacerbations in children.The Journal of allergy and clinical immunology · 2023Article
- Siglecs in allergy and asthma.Molecular aspects of medicine · 2023Review
- Drug delivery targets and strategies to address mast cell diseases.Expert opinion on drug delivery · 2023Review
- Does SIGLEC8 localize to the subcellular compartment like the Alzheimer's disease protective CD33 splice variant?Frontiers in cellular neuroscience · 2023Article
- Interactions between Siglec-8 and endogenous sialylated cis ligands restrain cell death induction in human eosinophils and mast cells.Frontiers in immunology · 2023Article
- Discovery of an agonistic Siglec-6 antibody that inhibits and reduces human mast cells.Communications biology · 2022Article
- Article
- Proceedings from the Inaugural American Initiative in Mast Cell Diseases (AIM) Investigator Conference.The Journal of allergy and clinical immunology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSialic acid-binding immunoglobulin-like lectin (Siglec)-8 is a cell-surface protein expressed selectively on human eosinophils, mast cells, and basophils, making it an ideal target for the treatment of diseases involving these cell types. However, the effective delivery of therapeutic agents to these cells requires an understanding of the dynamics of Siglec-8 surface expression.
objectivesWe sought to determine whether Siglec-8 is endocytosed in human eosinophils and malignant mast cells, identify mechanisms underlying its endocytosis, and demonstrate whether a toxin can be targeted to Siglec-8-bearing cells to kill these cells.
methodsSiglec-8 surface dynamics were examined by flow cytometry using peripheral blood eosinophils, mast cell lines, and Siglec-8-transduced cells in the presence of inhibitors targeting components of endocytic pathways. Siglec-8 intracellular trafficking was followed by confocal microscopy. The ribosome-inhibiting protein saporin was conjugated to a Siglec-8-specific antibody to examine the targeting of an agent to these cells through Siglec-8 endocytosis.
resultsSiglec-8 endocytosis required actin rearrangement, tyrosine kinase and protein kinase C activities, and both clathrin and lipid rafts. Internalized Siglec-8 localized to the lysosomal compartment. Maximal endocytosis in Siglec-8-transduced HEK293T cells required an intact immunoreceptor tyrosine-based inhibitory motif. Siglec-8 was also shuttled to the surface via a distinct pathway. Sialidase treatment of eosinophils revealed that Siglec-8 is partially masked by sialylated cis ligands. Targeting saporin to Siglec-8 consistently caused extensive cell death in eosinophils and the human mast cell leukemia cell line HMC-1.2.
conclusionsTherapeutic payloads can be targeted selectively to eosinophils and malignant mast cells by exploiting this Siglec-8 endocytic pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.