LUNG VASCULAR & CELLULAR ACTIONS OF C3A, C5A, & FMLP

肺血管

• 批准号: 3087483
• 负责人: RICHARD E CROWELL
• 金额: $ 6.94万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087483
• 关键词: NAD(H) phosphate; adult respiratory distress syndrome; alveolar macrophages; aminopyridines; anaphylatoxins; antibody receptor; antihistamines; arachidonate; arginine; benzofurans; cardiovascular pharmacology; cimetidine; complement pathway; complement receptor; dimethylsulfoxide; eicosanoid metabolism; enzyme inhibitors; flow cytometry; fluorescent dye /probe; histamine release; histology; hydrogen peroxide; ibuprofen; immunoglobulin G; laboratory rabbit; methylprednisolone; oligopeptides; peptide analog; phagocytosis; phorbols; prostaglandin endoperoxide synthase; prostaglandins; pulmonary artery; pulmonary circulation; thromboxanes; vascular endothelium permeability; vasoconstriction

The adult respiratory distress syndrome (ARDS) is characterized by pulmonary vasoconstriction as well as accumulation of cells and protein-rich fluid within the lung parenchyma. The mechanisms of these abnormalities are not understood. C3a and C5a, the anaphylatoxin products of complement activation, and formaylated oligopeptide bacterial products (e.g. formyl methionine-leucine-phenylalanine; fMLP) may be important in the development of these abnormalities. In this proposal we will investigate the actions of C3a, C5a, and fMLP on isolated pulmonary artery segments and pulmonary macrophages from rabbits. The specific aims of this project are: 1. To determine if C3a, C5a, their des arg derivatives, or fMLP constrict isolated rabbit pulmonary artery ring segments. We will construct dose- response curves, and evaluate tissue desensitization, synergism, and cross-reactivity between these peptides. 2. To determine through the use of pharmacologic inhibitors if the actions of these peptides are attributable to the release of histamine or arachidonic acid metabolities. 3. To determine the role of endothelium in the actions of these peptides on isolated pulmonary artery segments by testing their effects on segments which have undergone mechanical denuding of endothelium. 4. To identify receptors for these peptides in pulmonary tissues utilizing fluorescent probes for C3a, C5a, and fMLP. 5. To analyze physical parameters, ligand binding characteristics, and functional properties of pulmonary macrophages through the use of multiparameter flow cytometry. These studies will broaden our understanding of cellular and vascular responses to C3a, C5a, and fMLP, and may result in the development of more effective therapeutic modalities for ARDS.

成人呼吸窘迫综合征（ARDS）的特点是 通过肺血管收缩以及细胞聚集 以及肺实质内富含蛋白质的液体。 的 这些异常的机制尚不清楚。 c3 a和 C5 a，补体激活的过敏毒素产物，以及 甲酰基化寡肽细菌产物（例如甲酰基 甲硫氨酸-亮氨酸-苯丙氨酸; fMLP）可能在 这些异常的发展。 在本提案中，我们将 研究C3 a、C5 a和fMLP对分离的 肺动脉段和肺巨噬细胞 家兔 该项目的具体目标是：1。以确定是否 C3 a、C5 a、其des arg衍生物或fMLP收缩分离 兔肺动脉环段。 我们将建造剂量- 响应曲线，并评估组织脱敏，协同作用， 以及这些肽之间的交叉反应性。 2.以确定 通过使用药理学抑制剂，如果这些药物的作用 肽可归因于组胺的释放， 花生四烯酸代谢 3.确定的作用 这些肽对血管内皮细胞的作用 肺动脉段，通过测试其对段的影响 其经历了内皮的机械剥脱。 4.到 鉴定肺组织中这些肽的受体， C3 a、C5 a和fMLP的荧光探针。 5.分析 物理参数、配体结合特性和功能 肺巨噬细胞的性质，通过使用 多参数流式细胞术 这些研究将扩大我们的 了解细胞和血管对C3 a，C5 a和 fMLP，并可能导致发展更有效的 ARDS的治疗方式。