A PRIMATE MODEL OF NEONATAL LUNG DEFENSE MECHANISMS

将采用狒狒模型来支持2个旨在研究 围产期发育过程中的局部肺防御机制：1） 肺巨噬细胞功能; 2）呼吸道屏障功能 管道上皮表面。 将在3个时间点研究胎狒狒 在妊娠晚期、足月和出生后1个月的时间点。 项目1将确定肺动脉栓塞出现的时间范围。 肺组织和肺泡腔中的巨噬细胞（PM）。 一个主要重点 将在第三个三个月期间定义PM的功能能力 生命的第一个月。 这将包括检查其吞噬细胞 和杀微生物潜力，产生免疫活性 淋巴细胞和抗原加工中的作用。 γ-干扰素会 研究其增强某些PM功能的能力。 单克隆 将产生狒狒淋巴细胞特异性抗体， 用于鉴定存在于淋巴细胞中的特定淋巴细胞亚类。 发育中的肺，并确定这些细胞与PM的相互作用。 的 呼吸道上皮及其分泌物形成了一个屏障， 潜在的病原体存在于外部环境中，它们可以保护 使宿主免于定植和感染。 项目2将研究 通过测量呼吸道上皮细胞的发育变化 表面碳水化合物模式。 这些模式将与 细菌粘附在上皮上。 呼吸道的影响 还将检查细菌结合的分泌物。 新生狒狒 重症监护病房，能够提供与现有病房类似的服务 为人类早产儿提供的服务。 因此，我们计划 研究早产和强化生命支持的影响（高P02， 孵育、机械通气）， 呼吸道上皮的屏障功能在一组中三分之一 三个月的狒狒胎儿

A baboon model will be employed to support 2 projects designed to study local pulmonary defense mechanisms during perinatal development: 1) pulmonary macrophage function; and, 2) the barrier function of respiratory tract epithelial surfaces. The fetal baboon will be studied at 3 time points during the third trimester, at term, and at 1 month after birth. Project 1 will establish the time frame for appearance of pulmonary macrophages (PM) in lung interstitium and alveolar spaces. A primary focus will be to define functional capabilities of PM during the third trimester and first month of life. This will include examination of their phagocytic and microbicidal potential, capacity for generation of immunocompetent lymphocytes, and role in antigen processing. Gamma-interferon will be studied for its ability to enhance certain PM functions. Monoclonal antibodies specific for baboon lymphocytes will be produced and they will be used to identify specific lymphocyte subclasses present in the developing lung and to define interactions of these cells with PM. The respiratory tract epithelium and its secretions form a barrier against potential pathogens present in the external environment and they protect the host from colonization and infection. Project 2 will study developmental changes in the respiratory tract epithelium by measuring surface carbohydrate patterns. These patterns will be correlated with bacterial adherence to the epithelium. Effects of respiratory tract secretions on bacterial binding also will be examined. A baboon neonatal intensive care unit capable of providing services similar to those provided for human prematures is available for this project. Therefore, we plan to study effects of premature delivery and intensive life support (high p02, incubation, mechanical ventilation) on both PM function and also the barrier function of the respiratory epithelium in a group of mid-third trimester fetal baboons.