The proliferation-inhibiting effect of endotoxin on human endothelial cells in culture and its possible implication in states of shock.
The aim of this study was to determine whether bacterial endotoxin (LPS) could be responsible for the in vitro endothelial proliferation-inhibiting activity found in some serum samples derived from patients suffering from "sepsis" or "shock." DNA-synthesis response of cultured human endothelial cells was measured by autoradiographic methods. We found a dose-dependent decrease in the proliferation-inducing capacity of human serum after the addition of endotoxin without any detectable cellular injury. This effect depended on the serum concentration in the culture medium: higher serum concentrations reduced the measurable LPS-activity. The endotoxin effect turned out to be preventable when LPS sera were preincubated with different concentrations of Polymyxin B sulphate. That treatment also seemed to prevent the inhibiting effect of some patient sera. The inhibiting effect of both the LPS-serum and the patient serum could be reversed by washing and adding fresh human serum. We conclude that the endothelial regeneration-inhibiting activity of endotoxin may play an important role in the irreversibility of certain shock states.
D001345:Autoradiography; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D011112:Polymyxin B / Q000494:pharmacology; D012475:Salmonella; D012772:Shock, Septic / Q000097:blood*; D013936:Thymidine / Q000378:metabolism; D014471:Umbilical Veins / Q000187:drug effects*
D004731:Endotoxins; D011112:Polymyxin B; D013936:Thymidine