George S E, Kohan M J, Gilmour M I, Taylor M S, Brooks H G, Creason J P, Claxton L D
Genetic Toxicology Division (MD 68A), U. S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Appl Environ Microbiol. 1993 Nov;59(11):3585-91. doi: 10.1128/aem.59.11.3585-3591.1993.
The environmental release of engineered microorganisms has caused health and environmental concerns. In this study, an animal model was used to examine health effects following pulmonary exposure to environmental and clinical isolates. In order to rule out the possibility that an adverse response was caused by endotoxin, 50% lethal doses (LD50) were determined, when possible, with endotoxin-sensitive (C3HeB/FeJ) and endotoxin-resistant (C3H/HeJ) mice by using both environmental isolates (Pseudomonas aeruginosa BC16, BC17, BC18, and AC869 and Pseudomonas maltophilia BC6) and clinical isolates (P. aeruginosa PAO1 and DG1). The LD50 of strains AC869, DG1, and PAO1 are 1.05 x 10(7), 6.56 x 10(6), and 1.02 x 10(7) CFU, respectively, in C3HeB/FeJ mice and 1.05 x 10(7), 1.00 x 10(7), and 2.75 x 10(6) CFU, respectively, in C3H/HeJ mice. Strains BC17 and BC18 were not lethal to the animals. On the basis of the LD50 data, an appropriate sublethal dose (approximately 10(6) CFU) was selected. Animals were challenged intranasally with microorganisms, and clearance from the lungs and nasal cavity was determined. Strains BC17, BC18, and AC869 were not detected in lungs or nasal washes 14 days following treatment. Strains BC6, BC16, and DG1 were recovered from the nasal cavities at the end of the experiment. Only strain PAO1 was detected in lungs and in nasal cavities 14 days after treatment. At selected intervals following treatment, the percentages of polymorphonuclear leukocytes and lymphocytes in bronchoalveolar lavage samples were determined. P. aeruginosa AC869, PAO1, and DG1 elicited a relatively strong inflammatory response which was indirectly related to lung clearance.(ABSTRACT TRUNCATED AT 250 WORDS)
工程微生物的环境释放引发了对健康和环境的担忧。在本研究中,使用动物模型来检测肺部暴露于环境分离株和临床分离株后的健康影响。为了排除内毒素引起不良反应的可能性,在可能的情况下,通过使用环境分离株(铜绿假单胞菌BC16、BC17、BC18和AC869以及嗜麦芽窄食单胞菌BC6)和临床分离株(铜绿假单胞菌PAO1和DG1),对内毒素敏感(C3HeB/FeJ)和内毒素耐受(C3H/HeJ)小鼠测定50%致死剂量(LD50)。菌株AC869、DG1和PAO1在C3HeB/FeJ小鼠中的LD50分别为1.05×10(7)、6.56×10(6)和1.02×10(7) CFU,在C3H/HeJ小鼠中的LD50分别为1.05×10(7)、1.00×10(7)和2.75×10(6) CFU。菌株BC17和BC18对动物无致死性。根据LD50数据,选择了合适的亚致死剂量(约10(6) CFU)。动物经鼻用微生物进行攻击,并测定肺部和鼻腔的清除情况。治疗14天后,在肺部或鼻腔灌洗液中未检测到菌株BC17、BC18和AC869。实验结束时,从鼻腔中回收了菌株BC6、BC16和DG1。治疗14天后,仅在肺部和鼻腔中检测到菌株PAO1。在治疗后的选定时间间隔,测定支气管肺泡灌洗样本中多形核白细胞和淋巴细胞的百分比。铜绿假单胞菌AC869、PAO1和DG1引发了相对较强的炎症反应,这与肺部清除间接相关。(摘要截断于250字)