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Pulmonary clearance and inflammatory response in C3H/HeJ mice after intranasal exposure to Pseudomonas spp
S E George1, M J Kohan, M I Gilmour
1Genetic Toxicology Division (MD 68A), U. S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Abstract:
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)
Insights
Environmental release of Pseudomonas aeruginosa and Pseudomonas maltophilia can pose health risks. This study found that P. aeruginosa strain PAO1 persisted in lungs and nasal cavities, eliciting an inflammatory response, unlike other tested strains.
Area of Science:
- Microbiology
- Environmental Health
- Toxicology
Background:
- Engineered microorganisms' environmental release raises health and ecological concerns.
- Pulmonary exposure to environmental and clinical bacterial isolates requires health effect assessment.
- Endotoxin's role in adverse responses necessitates using endotoxin-sensitive and resistant animal models.
Purpose of the Study:
- To evaluate health effects of pulmonary exposure to environmental and clinical bacterial isolates.
- To determine the lethality and clearance of various Pseudomonas strains in an animal model.
- To assess the inflammatory response elicited by different bacterial isolates following exposure.
Main Methods:
- Determined 50% lethal doses (LD50) of environmental (Pseudomonas aeruginosa, Pseudomonas maltophilia) and clinical isolates using endotoxin-sensitive and resistant mice.
- Selected sublethal doses for intranasal challenge and monitored bacterial clearance from lungs and nasal cavities over 14 days.
- Analyzed bronchoalveolar lavage samples to determine inflammatory cell percentages (polymorphonuclear leukocytes, lymphocytes).
Main Results:
- Pseudomonas aeruginosa strains AC869, DG1, and PAO1 exhibited varying LD50 values in different mouse strains.
- Pseudomonas aeruginosa strain PAO1 was the only strain detected in lungs and nasal cavities 14 days post-exposure.
- P. aeruginosa strains AC869, PAO1, and DG1 induced significant inflammatory responses, indirectly correlating with lung clearance.
Conclusions:
- Pseudomonas aeruginosa strain PAO1 demonstrates persistence and elicits an inflammatory response after pulmonary exposure.
- Clearance and inflammatory potential vary significantly among different environmental and clinical Pseudomonas isolates.
- Understanding strain-specific behavior is crucial for assessing health risks associated with microbial environmental release.