ArticleThe Journal of biological chemistry2012
Hyaluronan anchored to activated CD44 on central nervous system vascular endothelial cells promotes lymphocyte extravasation in experimental autoimmune encephalomyelitis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- The CEMIP Hyaluronidase is Elevated in Oligodendrocyte Progenitor Cells and Inhibits Oligodendrocyte Maturation.ASN neuro · 2025Article
- Article
- Cytoprotective E-WE thrombin reduces disease severity in a murine model of relapsing-remitting multiple sclerosis.American journal of physiology. Cell physiology · 2024Article
- Centella asiatica promotes antioxidant gene expression and mitochondrial oxidative respiration in experimental autoimmune encephalomyelitis.Research square · 2023Article
- The Heterogeneous Multiple Sclerosis Lesion: How Can We Assess and Modify a Degenerating Lesion?International journal of molecular sciences · 2023Review
- Identification of age-specific gene regulators of La Crosse virus neuroinvasion and pathogenesis.Nature communications · 2023Article
- Age influences susceptibility of brain capillary endothelial cells to La Crosse virus infection and cell death.Journal of neuroinflammation · 2021Article
- Diverse Roles for Hyaluronan and Hyaluronan Receptors in the Developing and Adult Nervous System.International journal of molecular sciences · 2020Review
- Spheroids of Endothelial Cells and Vascular Smooth Muscle Cells Promote Cell Migration in Hyaluronic Acid and Fibrinogen Composite Hydrogels.Research (Washington, D.C.) · 2020Article
- Neuronal maturation reduces the type I IFN response to orthobunyavirus infection and leads to increased apoptosis of human neurons.Journal of neuroinflammation · 2019Article
- Hyaluronan impairs the barrier integrity of brain microvascular endothelial cells through a CD44-dependent pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Article
- Hyaluronan in immune dysregulation and autoimmune diseases.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Potential Roles of CD34+ Fibrocytes Masquerading as Orbital Fibroblasts in Thyroid-Associated Ophthalmopathy.The Journal of clinical endocrinology and metabolism · 2019Review
- The extracellular matrix of the blood-brain barrier: structural and functional roles in health, aging, and Alzheimer's disease.Tissue barriers · 2019Review
- Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers?Frontiers in immunology · 2018Article
- CD44 deletion leading to attenuation of experimental autoimmune encephalomyelitis results from alterations in gut microbiome in mice.European journal of immunology · 2017Article
- Microvasculature of the Mouse Cerebral Cortex Exhibits Increased Accumulation and Synthesis of Hyaluronan With Aging.The journals of gerontology. Series A, Biological sciences and medical sciences · 2017Article
- Role of Anti-Osteopontin Antibodies in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.Frontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The extravasation of lymphocytes across central nervous system (CNS) vascular endothelium is a key step in inflammatory demyelinating diseases including multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). The glycosaminoglycan hyaluronan (HA) and its receptor, CD44, have been implicated in this process but their precise roles are unclear. We find that CD44(-/-) mice have a delayed onset of EAE compared with wild type animals. Using an in vitro lymphocyte rolling assay, we find that fewer slow rolling (<1 μm/s) wild type (WT) activated lymphocytes interact with CD44(-/-) brain vascular endothelial cells (ECs) than with WT ECs. We also find that CD44(-/-) ECs fail to anchor HA to their surfaces, and that slow rolling lymphocyte interactions with WT ECs are inhibited when the ECs are treated with a pegylated form of the PH20 hyaluronidase (PEG-PH20). Subcutaneous injection of PEG-PH20 delays the onset of EAE symptoms by ~1 day and transiently ameliorates symptoms for 2 days following disease onset. These improved symptoms correspond histologically to degradation of HA in the lumen of CNS blood vessels, decreased demyelination, and impaired CD4(+) T-cell extravasation. Collectively these data suggest that HA tethered to CD44 on CNS ECs is critical for the extravasation of activated T cells into the CNS providing new insight into the mechanisms promoting inflammatory demyelinating disease.
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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.