Induction of Mucosal Tolerance to E-Selectin Prevents Ischemic and Hemorrhagic Stroke in Spontaneously Hypertensive Genetically Stroke-Prone Rats
| العنوان: | Induction of Mucosal Tolerance to E-Selectin Prevents Ischemic and Hemorrhagic Stroke in Spontaneously Hypertensive Genetically Stroke-Prone Rats |
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| المؤلفون: | John M. Hallenbeck, Richard M. McCarron, Hidetaka Takeda, Maria Spatz, Kyra J. Becker, Christl A. Ruetzler |
| المصدر: | Stroke. 33:2156-2164 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Lipopolysaccharides, Lipopolysaccharide, Ovalbumin, medicine.medical_treatment, Drug Evaluation, Preclinical, Brain Ischemia, chemistry.chemical_compound, Antigen, Rats, Inbred SHR, Immune Tolerance, medicine, Animals, Genetic Predisposition to Disease, Hypersensitivity, Delayed, Lymphocytes, Immunity, Mucosal, Immunologic Tolerance, Stroke, Cerebral Hemorrhage, Cerebral Cortex, Advanced and Specialized Nursing, biology, business.industry, Immunosuppression, medicine.disease, Thrombosis, Immunity, Innate, Rats, Survival Rate, Nasal Mucosa, Instillation, Drug, Treatment Outcome, chemistry, Immunology, biology.protein, Nasal administration, Neurology (clinical), E-Selectin, Cardiology and Cardiovascular Medicine, business |
| الوصف: | Background and Purpose— Inflammatory and immune mechanisms can precipitate cerebrovascular thrombosis and hemorrhage. Immunologic tolerance can be induced to a specific antigen by intranasal instillation of that antigen. Lymphocytes tolerized in this way provide local immunosuppression on restimulation with the same antigen. This study tests whether tolerization of lymphocytes to E-selectin can suppress local vessel activation and prevent stroke. Methods— Spontaneously hypertensive genetically stroke-prone rats (n=113) were distributed among the following studies: comparison of ischemic infarcts/intraparenchymal hemorrhages after single or repetitive tolerization schedules with ovalbumin, E-selectin, or PBS; comparison of E-selectin tolerization– and PBS tolerization–induced suppression of delayed-type hypersensitivity in animals subsequently sensitized to E-selectin; and comparison of PBS–, ovalbumin–, and E-selectin–tolerized groups (after intravenous lipopolysaccharide to activate vessels) regarding transforming growth factor-β1–positive splenocyte counts, plasma interferon-γ levels, anti-human E-selectin antibodies, endothelial intercellular adhesion molecule-1, and anti–endothelial cell antibodies. Results— Nasal instillation of E-selectin, which is specifically expressed on activated endothelium, potently inhibited the development of ischemic and hemorrhagic strokes in spontaneously hypertensive stroke-prone rats with untreated hypertension. Repeated schedules of tolerization were required to maintain the resistance to stroke. Suppression of delayed-type hypersensitivity to E-selectin and increased numbers of transforming growth factor-β1–positive splenocytes showed that intranasal exposure to E-selectin induced immunologic tolerance. E-selectin tolerization also reduced endothelial activation and immune responses after intravenous lipopolysaccharide, as shown by marked suppression of intercellular adhesion molecule-1 expression, anti–endothelial cell antibodies on luminal endothelium, and plasma interferon-γ levels compared with the control condition. Conclusions— The novel findings in this study support further investigation of immunologic tolerance as applied to the prevention of stroke. |
| تدمد: | 1524-4628 0039-2499 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::50bceabca74707ca5fea9863958a91f9 https://doi.org/10.1161/01.str.0000029821.82531.8b |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....50bceabca74707ca5fea9863958a91f9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244628 00392499 |
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