title: Pathology of lethal and sublethal doses of aerosolized ricin in rhesus macaques.
abstract: Ricin toxin, a type 2 ribosome-inactivating protein and a category B bioterrorism agent, is produced from the seeds of castor oil plant (Ricinus communis). Chronic pathological changes in survivors of aerosolized ricin exposure have not been reported in primates. Here we compare and contrast the pathological changes manifested between rhesus macaques (RM) that succumbed to lethal dose of ricin (group I) and survivor RM exposed to low dose of ricin (group II). All animals in group I exhibited severe diffuse, necrotizing bronchiolitis and alveolitis with fibrinopurulent bronchointerstitial pneumonia, massive alveolar, perivascular and peribronchial/bronchiolar edema with hemorrhage, and necropurulent and hemorrhagic tracheobronchial lymphadenitis. All animals from group II had multifocal, fibrosing interstitial pneumonia with prominent alveolar histiocytosis and type II pneumocyte hyperplasia. Subacute changes like infiltration by lymphocytes and plasma cells and persistence of edematous fluid were occasionally present in lung and tracheobronchial lymph nodes. The changes appear to be a continuum wherein the inflammatory response shifts from an acute to subacute/chronic reparative process if the animals can survive the initial insult.
authors.affiliation: 1Infectious Disease Aerobiology, Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Manoj
authors.initials: M
authors.lastname: Bhaskaran
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Didier
authors.forename: Satheesh K
authors.initials: SK
authors.lastname: Sivasubramani
authors.forename: Lara A
authors.initials: LA
authors.lastname: Doyle
authors.forename: Jane
authors.initials: J
authors.lastname: Holley
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008253:Macaca mulatta; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology; D012276:Ricin / Q000008:administration & dosage / Q000633:toxicity; D018675:Toxicity Tests; D059551:Toxicity Tests, Subacute
chemical_list: D000336:Aerosols; D012276:Ricin
keywords: animal models; inhalation; nonhuman primate pathology; pulmonary; toxicity.