Prevention of paraquat toxicity in suspensions of alveolar type II cells by paraquat-specific antibodies.
1. The herbicide, paraquat, is accumulated by the energy-dependent polyamine uptake pathway of alveolar type II cells. There it undergoes redox cycling that results in an amplified production of toxic reactive oxygen species and depletion of NADPH and other reducing equivalents. These processes account for the lung being the major target organ for paraquat toxicity. 2. We postulated that paraquat-specific antibodies would inhibit the uptake of the herbicide by type II cells and prevent its toxicity. Accordingly, we examined the effects of paraquat-specific monoclonal antibodies and Fab fragments on the uptake, efflux and cytotoxicity of 50 microM paraquat in suspensions of alveolar type II cells isolated from the rat. 3. The uptake of paraquat was linear over 40 min. Over this time, the uptake rate was inhibited significantly (% inhibition, 73-89) by IgG (25 or 50 microM) or Fab fragments (50 or 100 microM). 4. The apparent efflux rate of paraquat, studied over 16 h, was increased significantly from 0.12 h-1 for the control cells in medium to 0.17 h-1 by paraquat-specific Fab fragments but was unaffected by the specific IgG. 5. Cytotoxicity was determined by measuring the release of 51Cr from the cells. The cytotoxicity of 50 microM paraquat was decreased significantly (percent decrease, 56-80%) in the presence of specific antibodies. 6. These studies in vitro suggest some potential for immunotherapy in selected cases of paraquat poisoning.
Chen
N
N
University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia.
Bowles
M R
MR
Pond
S M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000918:Antibody Specificity; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology* / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000276:immunology* / Q000627:therapeutic use; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010269:Paraquat / Q000276:immunology / Q000633:toxicity*; D011041:Poisoning / Q000517:prevention & control; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D002857:Chromium; D010269:Paraquat