In vitro and in vivo association and subcellular distribution of toxic and experimentally modified endotoxin.
Cell association and organ distribution of toxic and experimentally modified endotoxin were compared in whole animals and hepatoma tissue culture (HTC) cells. For both toxic and poly-l-alpha-ornithine mixed endotoxin in vivo, most of the endotoxin becomes associated with the reticuloendothelial system (RES) rich organs. Organ distribution does not change from 1 to 5 h. Significantly less detoxified endotoxin becomes associated with RES-rich organs. Association and nuclear transfer of toxic endotoxin in HTC cells are gradual and time-dependent processes. Plasma treatment increased association of endotoxin with HTC cells. Poly-l-alpha-ornithine (4 micrograms/mL) also significantly increases HTC cell association of endotoxin, and nuclear transfer of endotoxin was similar in principle to the toxic material. Association of detoxified endotoxin with HTC cells is significantly higher than toxic endotoxin and increases with time. In contrast with toxic and poly-l-alpha-ornithine mixed endotoxin, nuclear association of alkaline-treated detoxified endotoxin did not increase significantly during 5 h incubation. Cumulatively, these observations indicate that while tissue culture cells could provide a more controllable experimental system by which to study the fate and pathogenic mechanism of endotoxin at the cellular and subcellular level, HTC cells under the conditions employed herein do not yield binding data which compare favorably with in vivo results. Caution must be exercised when extrapolating in vitro data to the actual in vivo action of endotoxin.
D000818:Animals; D002500:Centrifugation, Isopycnic; D002860:Chromium Radioisotopes; D004731:Endotoxins / Q000378:metabolism* / Q000633:toxicity; D006868:Hydrolysis; D007928:Lethal Dose 50; D008033:Limulus Test; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D010949:Plasma; D014018:Tissue Distribution; D014461:Ultracentrifugation
D002860:Chromium Radioisotopes; D004731:Endotoxins