Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins.
Toxicity of lipopolysaccharide (LPS) (endotoxin) is, to a large extent, mediated by the activation of monocytes/macrophages and subsequent release of monokines, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). It is known that LPS binds readily to serum lipoproteins and that LPS-lipoprotein complexes are less toxic than unbound LPS. Here we present data analyzing the impact of the LPS-serum interaction at the cellular level. By measuring IL-1 TNF-alpha, and IL-6, the interaction of different LPSs or lipid A with human serum could be shown to prevent the activation of human monocytes. The amounts of LPS inactivated by normal human serum did not exceed 10 ng/ml. The LPS-inactivating capacity of serum was shown to be a function of the lipoproteins. Other serum components, such as naturally occurring anti-LPS immunoglobulin G, complement, or nutritive lipids, had no significant influence in our system. Our experiments suggest that serum lipoproteins control endotoxin-induced monocyte activation and monokine release.
Flegel
W A
WA
DRK-Blutspendezentrale, Universität Ulm, Federal Republic of Germany.
Wölpl
A
A
Männel
D N
DN
Northoff
H
H
D000907:Antibodies, Bacterial / Q000502:physiology; D002784:Cholesterol / Q000008:administration & dosage / Q000097:blood; D003165:Complement System Proteins / Q000502:physiology; D004041:Dietary Fats / Q000008:administration & dosage / Q000097:blood; D004731:Endotoxins; D005227:Fatty Acids / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000502:physiology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology; D008074:Lipoproteins / Q000097:blood / Q000502:physiology*; D008262:Macrophage Activation; D013696:Temperature
D000907:Antibodies, Bacterial; D004041:Dietary Fats; D004731:Endotoxins; D005227:Fatty Acids; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D008074:Lipoproteins; D003165:Complement System Proteins; D002784:Cholesterol