A Mouse Model of Bovine Pneumonic Pasteurellosis: Dose Response, Temporal Evolution of Lesions and Effects of Arachidonic Acid Inhibitors (Indomethacin, Nordihydroguaiaretic Acid, Hydroxyurea).
Date of Award
Doctor of Philosophy (PhD)
Outbred Swiss Webster mice were used as an experimental model for bovine pneumonic pasteurellosis. Using light microscopy and transmission electron microscopy to evaluate lesions, it was determined that intrabronchial inoculation of Pasteurella haemolytica serotype 1 induces dose dependent pulmonary lesions in the mouse. Five x 10('7) colony forming units was the optimum dose which induced lesions and allowed survival for at least 24 hours. Using the optimum dose of inoculum, lesions were evaluated at different time points to determine when neutrophil influx into the lung first occurred. Four hours post inoculation was the minimum time required for neutrophil influx to be a significant component of the pulmonary lesions. Neutrophil involvement in pulmonary lesions induced by Pasteurella haemolytica infection was evaluated using the mouse model. Mice were inoculated with one of three inocula: (1) Pasteurella haemolytica, (2) carbon particles, (phagocytosis control), or (3) saline (negative control). Mice from each inoculation group were subdivided into groups receiving one of the following pretreatments: (1) none, (2) indomethacin, an inhibitor of cyclooxygenase, (3) nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, or (4) hydroxyurea (neutrophil depleted controls). Lesions were evaluated at 4 and 24 hours by light microscopy, transmission electron microscopy, serum and pulmonary lavage fluid enzyme level analysis, blood and lavage cell counts, and ultrastructural examination of pulmonary lavage cells. Morphologically, NDGA pretreated Pasteurella inoculated mice had less severe lesions at 4 and 24 hours than non-pretreated or indomethacin pretreated Pasteurella inoculated mice. Hydroxyurea pretreated mice had the least severe lesions of all groups except the saline inoculated controls. No detectable differences were seen in carbon phagocytosis among the 4 pretreatment groups at 4 or 24 hours. Beta-glucuronidase/lavage cell, elastase/lavage cell, and myeloperoxidase/lavage cell levels were all lower in NDGA pretreated Pasteurella inoculated mice than in the other pretreatment groups at 4 hours, however, these changes were not statistically significant. The trend continued at 24 hours with elastase/lavage cell, but not the other two enzymes. Modulation of release of the enzymes may have contributed to the decreased pulmonary lesions in NDGA pretreated Pasteurella inoculated mice seen at the morphologic level.
Pace, Lanny Wade, "A Mouse Model of Bovine Pneumonic Pasteurellosis: Dose Response, Temporal Evolution of Lesions and Effects of Arachidonic Acid Inhibitors (Indomethacin, Nordihydroguaiaretic Acid, Hydroxyurea)." (1986). LSU Historical Dissertations and Theses. 4199.