The effects of T-2 toxin on alveolar macrophage function in vitro.
T-2 toxin, a metabolite of several Fusarium species, is a mycotoxin of the trichothecene family which occurs in a variety of grains. Previous work in our laboratory showed that T-2 toxin is highly toxic to rat alveolar macrophages in vitro at submicromolar concentrations. The present investigation was undertaken to study the basis of the cytotoxic effects observed. The following parameters of macrophage function were measured: macromolecular synthesis, release of 51Cr, cellular ATP, phagocytosis, and alveolar macrophage "activation." The incorporation of radiolabeled leucine into acid-precipitable molecules was significantly inhibited within 1 hr of treatment at sublethal concentrations, although amino acid uptake was unaffected. Cell volume and release of 51Cr was unaffected by 0.1 microM T-2 toxin after 6 hr but evidence of significant leakage was seen after 18 hr treatment. The capacity of alveolar macrophages to phagocytize Saccharomyces cerevisiae and 3H-Staphylococcus aureus was significantly reduced whereas binding of 3H-S. aureus to the macrophage was not. Macrophage activation with endotoxin (Escherichia coli lipopolysaccharide) and mitogen-generated lymphokines, as monitored by incorporation of [14C]glucosamine, was significantly altered at 0.01 microM T-2 toxin. Thus, the data clearly demonstrate that T-2 is toxic to alveolar macrophage function in vitro and suggest that the primary mechanism of this toxicity is related to the inhibition of protein synthesis.
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002860:Chromium Radioisotopes / Q000378:metabolism; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D012717:Sesquiterpenes / Q000633:toxicity*; D013211:Staphylococcus aureus / Q000187:drug effects; D013605:T-2 Toxin / Q000633:toxicity*
D002860:Chromium Radioisotopes; D008070:Lipopolysaccharides; D008222:Lymphokines; D012717:Sesquiterpenes; D000255:Adenosine Triphosphate; D013605:T-2 Toxin