Acute Inflammation by Human Leukocytes in Human Skin Xenografts

人类皮肤异种移植物中人类白细胞的急性炎症

• 批准号: 7608580
• 负责人: STEPHEN E. MALAWISTA
• 金额: $ 4.87万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608580
• 关键词: Acute; Address; Attention; Autoimmune Diseases; Bacteria; Binding; Biodistribution; Biology; Blood Circulation; Canis familiaris; Categories; Cells; Cytoplasmic Granules; Doctor of Philosophy; Eligibility Determination; Heating; Home environment; Homing; Human; Infection; Inflammation; Inflammatory; Jordan; Laboratories; Lesion; Leukocytes; Long-Term Effects; Medicine; Membrane; Modeling; Mus; Parents; Pathology; Public Health; Research Personnel; Research Project Grants; Respiratory Burst; Rheumatology; SCID Beige Mouse; Skin; Skin graft; Study models; Tissues; Xenograft procedure; abstracting; cytokine; neutrophil; skin xenograft

P/F #60 - "Acute Inflammation by Human Leukocytes in Human Skin Xenografts" Stephen Malawista, MD (Rheumatology), Nancy Kirkiles-Smith, PhD (Pathology) Eligibility Category Established Investigator, new skin-related research project. Abstract: In this proposal an expert in neutrophil biology, Dr. Stephen Malawista, is turning his attention to the recruitment to and function of neutrophils in skin, taking advantage of human skin xenograph models in the YSDRC core laboratory operated by Drs. Jordan Pober and Nancy Kirkiles-Smith. Our aim is to create a model of acute human skin inflammation. In SCID/beige mice engrafted with human skin, it has been difficult to adoptively transfer whole human neutrophils. Their recruitment to human xenografts stimulated by agents injected intradermally will depend in part on their persistence in the circulation, and the study of longer-term effects may require repeated administration of neutrophils. To address this potential difficulty we will explore the use of human neutrophil cytoplasts, which are heat-induced membrane-bound fragments from neutrophils that maintain the locomotory and phagocytic capacity of the parent cell, and which in a dog model have been shown to home to inflammatory skin lesions with generally equal facility to that of intact neutrophils. Lacking lysosomal granules and the respiratory burst, they may be more robust in "foreign territory" than the intact cells. Thus a key aim will be to compare whole neutrophils and cytoplasts for lifetime in the circulation, biodistribution into mouse tissues, and homing into human skin grafts at baseline and following local activation, e.g. with LPS or with cytokines. Once the model is established, we will examine the capacity of cytoplasts to perform specific neutrophil functions such as clearance of bacteria. Relevance to public health Acute inflammation and its control are of great importance in Medicine - in infection, autoimmune disorders, and elsewhere. A good model for studying acute inflammation in human skin will be useful to workers in the field.

P/F #60 -“人类皮肤异种移植物中人类白细胞引起的急性炎症” Stephen Malawista，医学博士（流变学），Nancy Kirkiles-Smith，博士（病理学） 资格类别既定研究者，新皮肤相关研究项目。 翻译后摘要：在这个建议的专家在中性粒细胞生物学，斯蒂芬Malawista博士，是把他的注意力转向 中性粒细胞在皮肤中的募集和功能，利用人类皮肤异种移植模型， YSDRC核心实验室由Jordan Pober博士和Nancy Kirkiles-Smith博士操作。我们的目标是创造一个 急性人类皮肤炎症模型。在移植了人类皮肤的SCID/米色小鼠中， 来过继转移整个人类中性粒细胞它们在药物刺激下被募集到人类异种移植物中 皮内注射将部分取决于它们在循环中的持久性，以及长期研究。 作用可能需要反复给予嗜中性粒细胞。为了解决这个潜在的困难，我们将探讨 使用人嗜中性粒细胞胞质，其是来自嗜中性粒细胞的热诱导的膜结合片段， 维持母细胞的运动和吞噬能力，并且在狗模型中， 显示其归巢至炎性皮肤损伤，其功能与完整的中性粒细胞的功能大致相同。缺乏 溶酶体颗粒和呼吸爆发，他们可能更强大的“外国领土”比完整的 细胞因此，一个关键的目标将是比较整个中性粒细胞和细胞质在循环中的寿命， 生物分布到小鼠组织中，并在基线和局部活化后归巢到人皮肤移植物中， 例如LPS或细胞因子。一旦模型建立，我们将检查细胞质的能力， 执行特定的中性粒细胞功能，如清除细菌。 与公共卫生的相关性 急性炎症及其控制在医学中非常重要-在感染、自身免疫性疾病、 和其他地方。研究人类皮肤急性炎症的良好模型将对研究人员有用。 领域