The effect of immunosuppressants and adoptive transfer in monocrotaline pyrrole pneumotoxicity.
Monocrotaline pyrrole (MCTP) is a pyrrolizidine alkaloid that causes pulmonary vascular injury and pulmonary hypertension in rats. The lesions in lungs of MCTP-treated rats are similar to those occurring in humans with primary pulmonary hypertension. Thus, the MCTP-treated rat is a good animal model for this disease. The mechanisms by which MCTP causes lung injury are unknown. The character of the pulmonary lesions and the delay in onset of the injury after a single low dose of MCTP suggest that immune mechanisms may be important in the pathogenesis. Accordingly, rats were treated with MCTP and the immunosuppressants antilymphocyte serum (ALS) or cyclosporin A (CyA). Neither ALS nor CyA completely protected rats from the injury due to MCTP. Several series of experiments also were undertaken to assess the effect of lymphocytes adoptively transferred from MCTP-treated donor rats into MCTP-treated recipient rats. Adoptive transfer of lymphocytes did not decrease the onset time of the injury or increase the severity of lesions due to MCTP in the recipients. These results indicate that immune mechanisms are probably not involved in MCTP-induced pulmonary injury.
Bruner
L H
LH
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Bull
R W
RW
Roth
R A
RA
D000818:Animals; D000961:Antilymphocyte Serum / Q000276:immunology / Q000494:pharmacology; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000201:enzymology; D003524:Cyclosporins / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000276:immunology; D006984:Hypertrophy; D007116:Immunization, Passive; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D016686:Monocrotaline / Q000031:analogs & derivatives*; D009929:Organ Size; D011763:Pyrrolizidine Alkaloids / Q000276:immunology / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains
D000961:Antilymphocyte Serum; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D011763:Pyrrolizidine Alkaloids; C014114:monocrotaline pyrrole; D016686:Monocrotaline; D007770:L-Lactate Dehydrogenase