Lesions of Acute Inhaled Lethal Ricin Intoxication in Rhesus Monkeys

Wilhelmsen, Catherine L.; Pitt, M. Louise M.

doi:10.1177/030098589603300306

Cited by 105 publications

(97 citation statements)

References 13 publications

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“…4d). The histological lesions observed in these mice are consistent with an aerosolized ricin exposure, and generally represent the temporal progression of acute pulmonary toxicity described in other animals exposed to ricin via aerosol (Poli et al, 1996;Wilhelmsen and Pitt, 1996).…”

Section: Histopathologic Changes In the Lungssupporting

confidence: 73%

“…5a). Another physiological parameter monitored was the total body weight loss; it is known that ricin intoxicated animals suffer from significant weight loss (Wilhelmsen and Pitt, 1996). Indeed, a reduction of approximately 25% of the original weight was observed for BALB/c mice that inhaled ricin by 192 h. The mice that received the saline treatment maintained their original body weight and appeared to be healthy throughout the observation period (Fig.…”

Section: Physiological Changes In the Lungs Due To Ricin Toxicitymentioning

confidence: 99%

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Pulmonary gene expression profiling of inhaled ricin

DaSilva

Cote

Roy

et al. 2003

Toxicon

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Section: Histopathologic Changes In the Lungssupporting

confidence: 73%

Section: Physiological Changes In the Lungs Due To Ricin Toxicitymentioning

confidence: 99%

Pulmonary gene expression profiling of inhaled ricin

DaSilva

Cote

Roy

et al. 2003

Toxicon

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“…These data are consistent with previous reports on the histopathological effects of aerosolized ricin in animal systems. 20,21,[31][32][33] In addition, we have demonstrated that instilled ricin caused widespread nuclear localization of phosphorylated ERK, p38 MAPK, and JNK, but only phosphorylated p38 MAPK was evident in control lungs. These results are consistent with data obtained by immunoblotting, which demonstrated that ricin induced a large increase in phosphorylated JNK and ERK, but not p38 MAPK (Figure 3a).…”

Section: Discussionmentioning

confidence: 66%

Intrapulmonary Delivery of Ricin at High Dosage Triggers a Systemic Inflammatory Response and Glomerular Damage

Wong

Korcheva

Jacoby

et al. 2007

The American Journal of Pathology

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In view of the possibility that ricin may be used as a bioweapon against human populations, we examined the pathological consequences that occur in mice after introduction of ricin into the pulmonary system. Intratracheal instillation of a lethal dose of ricin (20 g/100 g body weight) resulted in a hemorrhagic inflammatory response in multiple organs, accompanied by activation of mitogen-activated protein kinases, increased synthesis of proinflammatory RNA transcripts, and increased levels of circulating cytokines and chemokines. A sublethal dose of instilled ricin (2 g/100 g body weight) induced a similar response in lungs but did not cause detectable damage in other organs. Lungs of mice that recovered from a sublethal dose of ricin displayed evidence of fibrosis and residual damage. A lethal dose of ricin caused accumulation of proinflammatory RNA transcripts and substantial damage to 28S rRNA of multiple organs, including lung, kidney, spleen, liver, and blood, demonstrating that instilled ricin gained access to the circulation. The kidneys of mice instilled with a lethal dose of ricin showed accumulation of fibrin/fibrinogen in glomerular capillaries, increased numbers of glomerular leukocytes, and impairment of kidney function. A sublethal dose of ricin failed to induce damage to 28S rRNA in kidney or other extrapulmonary organs.

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“…Animals were infected by aerosol at the U.S. Army Medical Research Institute of Infectious Diseases by using a nose-only system where aerosols are generated in a class III biosafety glove box cabinet under negative pressure or in a completely contained biosafety level 4 air-locked area. The biosafety level 3 exposure chamber was a 16-liter Plexiglas box with one side containing a circular latex dam with a cutout into which the nose and mouth of the rabbit were inserted (41). The aerosol was generated with a Collison nebulizer containing bacilli suspended in the 10% dilution of oleic albumin complex.…”

Section: Methodsmentioning

confidence: 99%

Different Strains ofMycobacterium tuberculosisCause Various Spectrums of Disease in the Rabbit Model of Tuberculosis

Manabe¹,

Dannenberg

Tyagi³

et al. 2003

Infect Immun

138

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The rabbit model of tuberculosis has been used historically to differentiate between Mycobacterium tuberculosis and Mycobacterium bovis based on their relative virulence in this animal host. M. tuberculosis infection in market rabbits is cleared over time, whereas infection with M. bovis results in chronic, progressive, cavitary disease leading to death. Because of the innate resistance of commercial rabbits to M. tuberculosis, 320 to 1,890 log-phase, actively growing inhaled bacilli were required to form one grossly visible pulmonary tubercle at 5 weeks. The range of inhaled doses required to make one tubercle allows us to determine the relative pathogenicities of different strains. Fewer inhaled organisms of the M. tuberculosis Erdman strain were required than of M. tuberculosis H37Rv to produce a visible lesion at 5 weeks. Furthermore, with the Erdman strain, only 7 of 15 rabbits had healed lesions at 16 to 18 weeks; among the other animals, two had chronic, progressive cavitary disease, a phenotype usually seen only with M. bovis infection. Genotypic investigation of the Erdman strain with an H37Rv-based microarray identified gene differences in the RD6 region. Southern blot and PCR structural genetic analysis showed significant differences between M. tuberculosis strains in this region. Correlation of the relative pathogenicity, including disease severity, in the rabbit model with the strain genotype may help identify stage-specific M. tuberculosis genes important in human disease.Tuberculosis continues to be a leading cause of infectious disease mortality. Because of the complex pathogenesis of the disease, the development of animal models for specific stages of disease such as latency and cavitation remains a priority. The murine model is the most widely used animal model because of its economy, the extensive characterization of inbred strains, and the commercial availability of immunologic reagents (31). The guinea pig is another well-researched model of tuberculosis and has the advantages of remarkable susceptibility to low doses of aerosolized Mycobacterium tuberculosis and the development of a strong delayed-type hypersensitivity response (11,36,37,40).The rabbit model offers certain advantages over both the murine and guinea pig models. First, when infected with M. tuberculosis or Mycobacterium bovis, rabbits have a spectrum of disease that represents many of the specific stages of human disease. In general, rabbits are able to contain disease caused by virulent M. tuberculosis. Over time, the number of pulmonary bacilli decline and the lesions regress (22). With M. bovis infection, rabbits form chronic fibrosing pulmonary cavities (8). Both of these are prominent features in human disease. Finally, rabbit lung granulomas, with their caseous centers, closely resemble the human granuloma. Lurie and colleagues have found a remarkable similarity between the spectrum of rabbit tuberculosis and that found in humans (23).In the era before genomics and before the biochemical property differences were elucid...

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Lesions of Acute Inhaled Lethal Ricin Intoxication in Rhesus Monkeys

Cited by 105 publications

References 13 publications

Pulmonary gene expression profiling of inhaled ricin

Pulmonary gene expression profiling of inhaled ricin

Intrapulmonary Delivery of Ricin at High Dosage Triggers a Systemic Inflammatory Response and Glomerular Damage

Different Strains ofMycobacterium tuberculosisCause Various Spectrums of Disease in the Rabbit Model of Tuberculosis

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