INHIBITORY EFFECT OF CYSTIC FIBROSIS SERUM ON PSEUDOMONAS PHAGOCYTOSIS BY RABBIT AND HUMAN ALVEOLAR MACROPHAGES
INHIBITORY EFFECT OF CYSTIC FIBROSIS SERUM ON PSEUDOMONAS PHAGOCYTOSIS BY RABBIT AND HUMAN ALVEOLAR MACROPHAGES
复制标题
囊性纤维化血清对兔和人肺泡巨噬细胞吞噬假单胞菌的抑制作用
作者：
M. Thomassen;B. Boxerbaum;C. Demko;Paula J Kuchenbrod;D. Dearborn;R. Wood
总结：本报告介绍了实验观察结果，表明囊性纤维化（CF）血清中存在抑制活性，这会损害家兔以及人肺泡巨噬细胞对铜绿假单胞菌的吞噬作用。在研究的49份患者血清样本中，40份始终显示≥ 60%的抑制，3份显示无抑制，6份在20-60%的假单胞菌吞噬抑制范围内。在平行研究中，S.金黄色葡萄球菌和CF血清对粘质杆菌无抑制作用。CF血清与正常血清的混合不能克服抑制作用，表明存在抑制因子，而不是缺乏必要的成分。将血清暴露于玻璃、冷冻血清一次或在56 ℃加热30分钟后，抑制活性不会丧失。推测：囊性纤维化患者的血清在体外选择性抑制肺泡巨噬细胞功能;体内这种抑制活性的表达可能会损害宿主对感染的有效控制。对该活性的起源、性质和病理生理作用的研究可能为控制假单胞菌肺部感染提供新的方法。脓疱性感染是囊性纤维化（CF）相关发病率和死亡率的主要因素（6）。假单胞菌是环境中的一种微生物，是囊性纤维化（CF）（6）。假单胞菌是环境中的一种常见微生物，对健康人无致病性。然而，患有慢性肺疾病CF的个体特别容易受到机会性铜绿假单胞菌感染。这种微生物在CF肺部感染中的频率解释不充分。众所周知，大多数CF患者的血清和肺分泌物中的假单胞菌抗体水平升高（12，14）。虽然最近有迹象表明，淋巴细胞对假单胞菌的无反应性可能是随着感染的进展而获得的（18，19），但没有一致观察到其他免疫异常（5.10）。肺外感染是非常罕见的，败血症几乎是从来没有，看到后的第一个月的生活（22）。这种不寻常的易感性，假单胞菌，尽管显然正常的全身体液和细胞免疫。提示CF中局部肺宿主防御机制存在缺陷。最近的几项研究表明，肺防御在一定程度上可以独立于全身体液和细胞介导的免疫系统发挥作用（9，15，20，21）。由于某些CF患者的粘膜纤毛运输受损（5）。细菌的清除变得更加依赖于吞噬细胞的有效作用。我们实验室（2）和比格尔等人（I）的先前研究表明，CF血清会损害兔肺泡巨噬细胞对假单胞菌的吞噬作用。本报告提出的实验观察表明，CF血清中存在的抑制活性，削弱了人以及兔肺泡巨噬细胞的吞噬假单胞菌。
Summary: This report presents experimental observations indicating the presence of an inhibitory activity in cystic fibrosis (CF) serum which impairs phagocytosis of Pseudomonas aeruginosa by rabbit as well as human alveolar macrophages. Of the 49 patient serum samples studied, 40 consistently showed ≥ 60% inhibition, 3 showed no inhibition and 6 were in the range of 20–60% inhibition of Pseudomonas phagocytosis. In parallel studies, the phagocytosis of S. aureus and S. marcescens was found not to be inhibited by CF serum. Mixing of CF serum with normal serum could not overcome the inhibitory effect, indicating the presence of an inhibitory factor rather than the lack of a necessary component. The inhibitory activity is not lost upon exposure of serum to glass, upon freezing the serum once, or upon heating at 56 C for 30 minutes.Speculation: The serum of cystic fibrosis patients selectively inhibits alveolar macrophage function in vitro; the expression of this inhibitory activity in vivo may compromise effective host control of infection. Investigation of the origin, nature and pathophysiologic role of the activity may suggest new approaches to the control of Pseudomonas pulmonary infection.Pultionary infection is a major factor in the morbidity and mortality associated with cystic fibrosis (CF) (6). Pseudomonas, a uhrquitous organism in the environment, is cystic fibrosis (CF) (6). Pseudomonas, a uhrquitous organism in the environment, is usually not pathogenic for healthy individuals. However, individuals with the chronic lung disease of CF are particularly susceptible to opportunistic Pseudomonas aeruginosa infections. The frequency of this organism in CF pulmonary infections is inadequately explained. It is well known that most CF patients have elevated levels of Pseudomonas antibodies in their sera and pulmonary secretions (l2,14). While recently there has been an indication that a lymphocyte unresponsiveness to Pseudomonas may be acquired as the infection progresses (18,19), no other immunologic abnormality has been consistendy observed (5.10). Extrapulmonary infection is extremely rare and sepsis is almost never, seen after the first months of life (22). This unusual susceptibility to Pseudomonas despite apparently normal systemic humoral and cellular immunity. suggests that local pulmonary host defense mechanisms are defective in CF. Several recent studies have indicated that lung defenses can, to a certain extent, function independently of systemic humoral and cell mediated immune systems (9,15,20,21).Lung defenses include mucociliary transport as well as phagocytic cells, lymphocytes, and immunoglobulin secretion. Since mucociliary transport in some CF patients is compromised (5). clearing of the bacteria becomes more dependent on the efficient action of the phagocytic cells. Previous studies in our laboratory (2) and by Biggar, et al. (I) have shown that CF serum impairs phagocytosis of Pseudomonas by rabbit alveolar macrophages. This report presents experimental observations indicating the presence of an inhibitory activity in CF serum which impairs phagocytosis of Pseudomonas by human as well as rabbit alveolar macrophages.