Relationship of Interactions Between Stroma-Free Hemoglobin and Bacterial Endotoxins (LPS) and Toxicity of SFH.
Annual rept. 1 Aug 94-31 Jul 95,
VETERANS ADMINISTRATION MEDICAL CENTER SAN FRANCISCO CA
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Multiple methods have been used to evaluate the role of bacterial endotoxin LPS in the observed toxicities of solutions of hemoglobin Hb. A series of physical measurements were performed to determine the effects of Hb on the LPS macromolecule. These included ultrafiltration, density centrifugation, precipitation, and gel filtration, as well as investigations specifically designed to evaluate binding of LPS by Hb and to determine whether complex formation occurs. The data support the conclusion that the interaction between LPS and Hb results in the formation of a complex. The formation of LPS-Hb complexes is associated with disaggregation of the LPS macromolecule and importantly, with marked enhancement of the biological activity of LPS. Enhancement of the biological activity of LPS has been shown in two independent biological systems, i.e., activation of the coagulation cascade of Limulus amebocyte lysate and stimulation of the production of tissue factor by human endothelial cells. Similar results have been shown for a wide variety of clinically relevant LPSs and for both purified, native HbA0 and alpha a-crosslinked Hb. Therefore, enhancement of the biological activity of LPS is not limited to the crosslinked Hb that we selected for this initial group of experiments.
- Medicine and Medical Research