Reversal of intracellular toxicity of the trichothecene mycotoxin T-2 with monoclonal antibody.
The trichothecene mycotoxin T-2 is a potent inhibitor of intracellular protein synthesis. We have previously shown that a mouse immunoglobulin G1 monoclonal antibody (15H6) specific for T-2 toxin can neutralize the in vitro protein synthesis inhibitory effect of the toxin in human B-lymphoblastoid cultures, and protect rats from lethal toxemia. We now report that these monoclonal antibodies can induce the net efflux of [3H]-T-2 toxin from poisoned human B-lymphoblastoid cells in vitro, and restore protein synthesis. Administration of the monoclonal antibodies (250 mg/kg) 30 min before infusion of a lethal dose (1 mg/kg) of T-2 toxin causes the sequestration of the toxin in the plasma compartment. When administered 35 min after T-2 toxin, a time when the bulk of toxin is in the tissues, the monoclonal antibodies facilitate the migration of toxin back into the plasma compartment. These data demonstrate that monoclonal antibodies can be of therapeutic value against an intracellular toxin.
Hunter
K W
KW
Department of Pediatrics, Uniformed Services University of the Health Sciences, F. Edward Hebert School of Medicine, Bethesda, Maryland.
Brimfield
A A
AA
Knower
A T
AT
Powell
J A
JA
Feuerstein
G Z
GZ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000992:Antitoxins / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013605:T-2 Toxin / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000992:Antitoxins; D013605:T-2 Toxin