ALVEOLAR MACROPHAGE--SURFACTANT INTERACTIONS

肺泡巨噬细胞（AM）是巨噬细胞中独特的， 它们的有丝分裂潜力，有氧代谢的使用， 吞噬作用和免疫调节功能模式。 的 人们对导致这种专门化的因素知之甚少。 这些细胞嵌入表面活性剂中，表面活性剂影响 AM的效应子和免疫调节功能。 确定表面活性剂改变AM的机制 功能将需要仔细检查发生的生化事件 在表面活性剂和细胞的相互作用过程中。 这些研究的重点是 表面活性剂对AM和Will抑菌活性的影响 测试以下假设：表面活性剂通过特异性结合AM 表面脱辅基蛋白受体并分布于溶酶体 在那里酶促反应导致其代谢为氨基酸 和脂肪酸;表面活性剂的结合、摄取和/或代谢 人AM的免疫抑制活性 通过以下方式：a.）抑制增强， 质膜，B.）氧化脂质的产生， inhibitory，c.）和/或调解人。 将对假设进行检验 根据以下具体目标：（1）为了确定 大鼠AM对表面活性剂的体外结合和摄取动力学; 2.） 以确定表面活性剂的细胞分布， 二棕榈酰磷脂酰胆碱（DPPC）被大鼠AM摄取后; 3.）第三章为了确定表面活性剂在被吸收后的代谢命运， 大鼠AM和免疫活性的伴随释放 调解员;和4.）来研究 人AM表面活性物质代谢和免疫调节 人AM淋巴细胞对可溶性刺激物反应。 很长的- 长期目标是将这些发现应用于疾病。 方法 包括细胞免疫学（淋巴细胞胚细胞生成， 白细胞介素-1活性，酶联免疫测定）和 生物化学（酶测定、125碘结合测定和 摄取、亚细胞分级分离、电泳、脂质分析）。

Alveolar macrophages (AM) are unique among macrophages in their mitotic potential, use of aerobic metabolism during phagocytosis, and pattern of immunoregulatory function. The factors leading to such specialization are poorly understood. These cells are embedded within surfactant and surfactant affects both effector and immunoregulatory functions of AM. Determination of the mechanisms by which surfactant alters AM function will require scrutiny of the biochemical events occurring during interaction of surfactant and cells. These studies focus on the effect of surfactant on suppressive activities of AM and will test the following hypotheses: surfactant binds to AM via specific surface apoprotein receptors and is distributed to lysosomes where enzymatic reactions lead to its metabolism to amino acids and fatty acids; binding, uptake and/or metabolism of surfactant by human AM contributes to the immunosuppressive activity of AM through the following: a.) enhancement of inhibition by plasma membranes, b.) production of oxidized lipids which are inhibitory, c.) and/or mediators. The hypotheses will be tested according to the following Specific Aims: 1.) to determine the in vitro binding and kinetics of uptake of surfactant by rat AM; 2.) to determine the cellular distribution of surfactant and dipalmitoyl phosphatidylcholine (DPPC) after uptake by rat AM; 3.) to determine the metabolic fate of surfactant after uptake by rat AM and the concomitant release of immunologically active mediators; and 4.) to examine the relationships between surfactant metabolism by human AM and immunoregulation by human AM of lymphocyte response to soluble stimuli. The long- term goal is to apply these findings to disease. Methodology includes cellular immunology (lymphocyte blastogenesis, assay of interleukin-1 activity, enzyme-linked immunoassay) and biochemistry (enzyme assays, assay of 125 Iodine binding and uptake, subcellular fractionation, electrophoresis, lipid analysis).