Pulmonary clearance and inflammatory response in C3H/HeJ mice after intranasal exposure to Pseudomonas spp.
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)
George
S E
SE
Genetic Toxicology Division (MD 68A), U. S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Kohan
M J
MJ
Gilmour
M I
MI
Taylor
M S
MS
Brooks
H G
HG
Creason
J P
JP
Claxton
L D
LD
D000818:Animals; D001709:Biotechnology; D001835:Body Weight; D004351:Drug Resistance; D004731:Endotoxins / Q000633:toxicity; D006801:Humans; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009296:Nasal Cavity / Q000382:microbiology; D009929:Organ Size; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology; D011549:Pseudomonas / Q000302:isolation & purification / Q000472:pathogenicity*; D011552:Pseudomonas Infections / Q000209:etiology* / Q000473:pathology; D013045:Species Specificity
D004731:Endotoxins