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

39 Citations (Scopus)

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
StatePublished - May 2007

Fingerprint

Ricin
Kidney
Lung
Body Weight
RNA
Mitogen-Activated Protein Kinases
Fibrin
Leukocyte Count
Chemokines
Fibrinogen
Fibrosis
Spleen
Cytokines

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Intrapulmonary delivery of ricin at high dosage triggers a systemic inflammatory response and glomerular damage. / Wong, John; Korcheva, Veselina; Jacoby, David; Magun, Bruce.

In: American Journal of Pathology, Vol. 170, No. 5, 05.2007, p. 1497-1510.

Research output: Contribution to journalArticle

@article{721147ef1a5342c19525289bc331d653,
title = "Intrapulmonary delivery of ricin at high dosage triggers a systemic inflammatory response and glomerular damage",
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.",
author = "John Wong and Veselina Korcheva and David Jacoby and Bruce Magun",
year = "2007",
month = "5",
doi = "10.2353/ajpath.2007.060703",
language = "English (US)",
volume = "170",
pages = "1497--1510",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Intrapulmonary delivery of ricin at high dosage triggers a systemic inflammatory response and glomerular damage

AU - Wong, John

AU - Korcheva, Veselina

AU - Jacoby, David

AU - Magun, Bruce

PY - 2007/5

Y1 - 2007/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34250807925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250807925&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2007.060703

DO - 10.2353/ajpath.2007.060703

M3 - Article

C2 - 17456757

AN - SCOPUS:34250807925

VL - 170

SP - 1497

EP - 1510

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 5

ER -