Intrapulmonary delivery of ricin at high dosage triggers a systemic inflammatory response and glomerular damage

John Wong, Veselina Korcheva, David Jacoby, Bruce Magun

Research output: Contribution to journalArticle

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Abstract

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 μg/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 μg/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.

Original languageEnglish (US)
Pages (from-to)1497-1510
Number of pages14
JournalAmerican Journal of Pathology
Volume170
Issue number5
DOIs
Publication statusPublished - May 2007

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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