Demonstration of an Interaction between Transferrin and Lipopolysaccharide – An in vitro Study

Abstract

Transferrin is reported to be a major lipopolysaccharide binding protein of human plasma, at least in vitro. By use of the limulus-amebocyte-lysate test the influence of transferrin on endotoxicity was studied. In the absence of any other protein human iron-free transferrin was able to strongly enhance endotoxicity in a concentration-dependent manner. Similar results were obtained when transferrin was added to primarily heat-inactivated plasma. Even in this assay the endotoxin recovery increased when transferrin was exogenously added. On the other hand, transferrin inhibited endotoxicity when inactivation of the plasma samples was performed after the addition of endotoxin and transferrin. These results lead to the conclusion that transferrin in fact interacts with lipopolysaccharide in a biologically important manner. In order to achieve neutralization of endotoxin, however, other plasma constituents are needed. The hypothetical function of transferrin is possibly a disaggregation of lipopolysaccharide micelles, following the interaction between the two molecules. The present data should justify further studies in order to clarify a possible benefit of the substitution of transferrin during gram-negative sepsis.

Determination of Endotoxin-Neutralizing Capacity of Plasma in Postsurgical Patients

“…The plasma levels of these pro teins interacting with endotoxin are differen tially regulated and not only influenced by endotoxin. In our previous studies we found that endotoxin binding proteins could en hance endotoxicity when tested without any EurSurgRcs 1996;28:130-139further protein or decrease endotoxicity when tested after adding to plasma [2][3][4], The ENC, therefore, seems to be a complex system which cannot be reduced to single plasma components. The determination of ENC, however, turned out to be a simple and reli able method reflecting a systemic endotoxin challenge and correlating with impending or gan failure.…”

Consequences of Interaction of a Lipophilic Endotoxin Antagonist with Plasma Lipoproteins

“…Briefly, the indicated concentrations of antagonists were added as 10ϫ stocks in 50 l of 5% dextrose in water, followed by the addition of 50 l of LPS (final concentration, 10 ng/ml), to 400 l of heparinized whole blood obtained from healthy volunteers (age, 18 to 51 years; weight, 50 to 105 kg) for a total of 500 l/well (final concentration of whole blood, 80%). After a 3-h incubation with gentle shaking at 37°C in a 5% CO 2 atmosphere, the plates were centrifuged at 1,000 ϫ g for 10 min at 4°C, and then the plasma was drawn off and frozen at Ϫ80°C. The plasma samples were analyzed for TNF-␣ by an enzyme-linked immunosorbent assay (Genzyme Corp., Cambridge, Mass.).…”

Acute phase proteins as promising biomarkers: Perspectives and limitations for human and veterinary medicine

“…Moreover, several other metal ions can be bound and transported . Besides this, Trf has lipopolysaccharide binding and signaling effects like Lf‐dimers. Tetramers of Trf exhibit phagocytosis activating effects .…”