Aerosolized specific antibody protects mice from lung injury associated with aerosolized ricin exposure.
Parenteral vaccination with ricin toxoid, although protective against death after a lethal aerosol ricin challenge, only partially protects against lung lesions. Therefore, we tested whether passive protection with aerosolized specific anti-ricin IgG (goat polyclonal, affinity-purified) could protect against both lethality and lung lesions in unvaccinated mice. Healthy CD-l mice were administered antibody (Ab) by small particle aerosol. Group 1 received non-specific control Ab (2160 mg/min/m3), and groups 2 and 3 received anti-ricin IgG (960 and 3280 mg/min/m3, respectively). Each group was challenged with a lethal dose of aerosolized ricin 1 hr after Ab exposure. All group 1 (control Ab) mice developed diffuse airway epithelial necrosis, with severe interstitial edema and inflammation involving all lung lobes, and died 48-96 hr post-challenge (PC). In contrast, in groups 2 and 3 at 24 hr PC, lung lesions were absent to very mild although there was rare epithelial necrosis in the upper airways in both groups. By 48 hr PC, necrosis of the tracheal epithelium and peritracheal inflammation were noted in some group 3 mice only. By 4 days PC, lungs and airways did not differ from cage controls in most group 2 and 3 mice. Weight gain in group 2 and 3 mice paralleled that of control mice. At 14 days PC, lungs were no different in controls than in group 3 mice. However, two non-survivors in group 3 had obstructions due to proximal airway epithelial damage. All group 2 mice survived, although a mild lymphoplasmacytic perivasculitis was present at 14 days PC which was not noted in the group 3 mice.
Toxinology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
M A
MA
Poli
V R
VR
Rivera
M L
ML
Pitt
P
P
Vogel
D000280:Administration, Inhalation; D000336:Aerosols / Q000009:adverse effects*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000918:Antibody Specificity; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects*; D055370:Lung Injury; D008297:Male; D051379:Mice; D009336:Necrosis; D010316:Particle Size; D011654:Pulmonary Edema / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D012276:Ricin / Q000008:administration & dosage / Q000633:toxicity*; D014611:Vaccination; D015430:Weight Gain / Q000187:drug effects
D000336:Aerosols; D000906:Antibodies; D007074:Immunoglobulin G; D012276:Ricin