Light microscopic and ultrastructural pathology of seminiferous tubules of rats given multiple doses of Pasteurella multocida group D protein toxin.

Male Holtzman rats were given subcutaneous doses of a purified Pasteurella multocida group D heat-labile toxin on alternate days for up to 22 days. Rats were necropsied at 18 days or 36 days (14 days after last dose of toxin) or when moribund, and testicles were taken for histologic and ultrastructural examination. Other selected tissues, including liver and spleen, were taken for histologic examination. Histologically, testicular and splenic lesions occurred more consistently and at much smaller doses when compared with lesions in other target organs such as liver. Testicular and splenic lesions were present in all rats (6/6) given 0.8 micrograms/kg toxin and were seen in some rats (1/6) given as little as 0.2 micrograms/kg toxin. Only 3/6 rats given 0.8 micrograms/kg toxin had hepatic lesions; no hepatic lesions were seen at doses of 0.2 micrograms/kg. Testicles from toxin-treated rats were smaller and weighed less than controls. Seminiferous tubules were moderately dilated and lined by polygonal sertoli cells. The normal spermatogenic maturation sequence and mature spermatids were absent, and many tubules contained multinucleate spermatocytes. Severely affected tubules were necrotic and mineralized. Ultrastructurally, there was necrosis of adluminal spermatocytes, multinucleate cell formation, and spaces between Sertoli cell plasma membranes. Testicular lesions were similar to those described for vitamin D-deficient rats, vitamin A-deficient rats, vasectomized rats, and rats given intravenous tumor necrosis factor; however, rats given lethal doses of toxin did not have elevated levels of TNF alpha activity.

Histopathologic and antibody responses of rabbits exposed to aerosols containing spores of Aspergillus fumigatus: comparison of single and multiple exposures.

Resistance to pulmonary aspergillosis was studied in groups of rabbits exposed to aerosolized spores of Aspergillus fumigatus for 15 minutes on successive days for a total of 10, 7, or 4 exposures or a single exposure. The results of the study demonstrated that exposure of rabbits to spores for 15 minutes on 10 successive days did not result in an accumulation of viable spores in excess of those present in the lungs of rabbits exposed a single time. The tissue response in the lungs of the rabbits exposed at multiple times was more intense than that in the rabbits exposed once, but resolution of the lesions occurred similarly in terms of time and completeness of resolution. The duration of the antibody response as determined by a passive hemagglutination test and by enzyme-linked immunosorbent assay correlated with the number of exposures to spores, in that rabbits exposed 10 or 7 times to aerosolized spores remained positive longer than did those exposed fewer times. The results of the precipitin tests in agar gel were negative in all the rabbits but one.

Effect of aflatoxin on phagocytosis of Aspergillus fumigatus spores by rabbit alveolar macrophages.

Rabbits were given dialy doses of aflatoxin B1 equivalents of 0.03, 0.05, 0.07, and 0.09 mg for a 2-week period. Macrophages were harvested at the end of the experimental period, and in vitro phagocytosis experiments were conducted using Aspergillus fumigatus spores as ingestion particles. Alveolar macrophages from rabbits given the above doses of aflatoxin had reduced phagocytic activity when compared with macrophages from control rabbits. Incorporation of serum from the aflatoxin-treated rabbits in the in vitro culture system resulted in less stimulation of phagocytosis by macrophages from control rabbits when compared with the same system incorporating control serum. Stimulation of phagocytosis by macrophages was least when both serum and macrophages from aflatoxin-treated rabbits were used in the in vitro system.