Pseudomonas aeruginosa exotoxin A inhibits proliferation of human bone marrow progenitor cells in vitro.
Pseudomonas aeruginosa exotoxin A, a potent inhibitor of eukaryotic protein synthesis, is produced in vivo during human infection. We tested the hypothesis that exotoxin A may be responsible for the leukopenia which sometimes accompanies pseudomonas disease by examining the in vitro toxicity of exotoxin A for human bone marrow granulocyte-macrophage progenitor cells (colony-forming units in culture [CFU-c] in the soft agar cloning system. Colony formation by freshly obtained marrow cells from five normal subjects was inhibited by exotoxin A in a concentration-dependent manner. The mean 50 and 100% inhibitory concentrations of toxin were 1.4 x 10(-10) and 1.4 x 10(-8) M, respectively, and significant inhibition was observed at a toxin concentration as low as 1.4 x 10(-13) M in two subjects. The inhibitory effect of exotoxin A on colony formation was specifically neutralized by antiserum to exotoxin A. Although mouse CFU-c were somewhat less sensitive to exotoxin A in vitro compared with human CFU-c, exotoxin A produced significant leukopenia in vivo in mice. These data suggest a possible mechanism for the leukopenia which sometimes occurs in human pseudomonas disease.
D036002:ADP Ribose Transferases; D000328:Adult; D001427:Bacterial Toxins; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005098:Exotoxins / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007958:Leukocyte Count; D008264:Macrophages / Q000166:cytology; D011550:Pseudomonas aeruginosa; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A