Buret A, Dunkley M L, Pang G, Clancy R L, Cripps A W
Australian Institute of Mucosal Immunology, Faculty of Medicine, University of Newcastle, Royal Newcastle Hospital, New South Wales, Australia.
Infect Immun. 1994 Dec;62(12):5335-43. doi: 10.1128/iai.62.12.5335-5343.1994.
The aims of this study were to assess the role played by alveolar macrophages, tumor necrosis factor alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha) in pulmonary immunity against Pseudomonas aeruginosa in animals that have been immunized via the gut-associated lymphoid tissue. Following intra-Peyer's patch immunization and subsequent intratracheal challenge with live bacteria, significantly enhanced bacterial clearance from the lungs correlated with an increase in bronchoalveolar neutrophils, increased recruitment and phagocytic activity of alveolar macrophages, and accelerated production of TNF-alpha in the bronchoalveolar space, while levels of IL-1 alpha remained low. Administration of recombinant TNF-alpha in physiological concentrations did not affect the proliferation of P. aeruginosa in vitro, but when given intratracheally to rats at the time of infection, recombinant TNF-alpha significantly increased bacterial clearance from the lungs. In these animals, phagocytic activity of bronchoalveolar neutrophils was enhanced, while the recruitment of alveolar macrophages and neutrophils remained unchanged. In acutely infected nonimmune animals, bronchoalveolar concentrations of soluble IL-1 alpha and TNF-alpha increased until the time of death. Levels of prostaglandin E2 and thromboxane B2 were similar in each experimental group. These results indicate that infection in immune animals enhanced both recruitment and phagocytic activity of alveolar macrophages as well as induced an accelerated production of TNF-alpha. In immune challenged animals, this cytokine enhanced the phagocytic activity of neutrophils and improved bacterial clearance from the lung. Levels of soluble IL-1 alpha and TNF-alpha in nonimmune rats increased consistently following infection until the time of death, thus implicating these cytokines in the pathogenesis of acute P. aeruginosa pneumonia.
本研究的目的是评估肺泡巨噬细胞、肿瘤坏死因子α（TNF-α）和白细胞介素-1α（IL-1α）在经肠道相关淋巴组织免疫的动物抵抗铜绿假单胞菌肺部免疫中所起的作用。在经派伊尔结免疫并随后经气管内用活细菌攻击后，肺部细菌清除显著增强，这与支气管肺泡中性粒细胞增加、肺泡巨噬细胞募集和吞噬活性增强以及支气管肺泡空间中TNF-α产生加速相关，而IL-1α水平仍然较低。给予生理浓度的重组TNF-α在体外不影响铜绿假单胞菌的增殖，但在感染时经气管内给予大鼠，重组TNF-α显著增加肺部细菌清除。在这些动物中，支气管肺泡中性粒细胞的吞噬活性增强，而肺泡巨噬细胞和中性粒细胞的募集保持不变。在急性感染的非免疫动物中，支气管肺泡中可溶性IL-1α和TNF-α的浓度一直增加直至死亡。每个实验组中前列腺素E2和血栓素B2的水平相似。这些结果表明，免疫动物中的感染增强了肺泡巨噬细胞的募集和吞噬活性，并诱导了TNF-α的加速产生。在免疫攻击的动物中，这种细胞因子增强了中性粒细胞的吞噬活性并改善了肺部细菌清除。感染后，非免疫大鼠中可溶性IL-1α和TNF-α的水平持续增加直至死亡，因此提示这些细胞因子参与急性铜绿假单胞菌肺炎的发病机制。
