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 B.
AU - Magun, Bruce
N1 - Funding Information:
Supported by the National Institutes of Health (grants ES889456 and AI1059335 ).
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
SN - 0002-9440
VL - 170
SP - 1497
EP - 1510
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -