Accession Number : ADA303516

Title :   Relationship of Interactions Between Stroma-Free Hemoglobin and Bacterial Endotoxins (LPS) and Toxicity of SFH.

Descriptive Note : Annual rept. 1 Aug 94-31 Jul 95,

Corporate Author : VETERANS ADMINISTRATION MEDICAL CENTER SAN FRANCISCO CA

Personal Author(s) : Levin, Jack

PDF Url : ADA303516

Report Date : 15 SEP 1995

Pagination or Media Count : 125

Abstract : 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.

Descriptors :   *TOXICITY, *HEMOGLOBIN, *BACTERIAL TOXINS, *ENDOTOXINS, *LIPOPOLYSACCHARIDES, DENSITY, MEASUREMENT, ACTIVATION, STIMULATION(GENERAL), PRODUCTION, BIOLOGY, HUMANS, PHYSICAL PROPERTIES, BACTERIA, PRECIPITATION, ERYTHROCYTES, CELLS(BIOLOGY), GELS, CENTRIFUGE SEPARATION, FILTRATION, COAGULATION, ENDOTHELIUM, ULTRAFILTRATION.

Subject Categories : Medicine and Medical Research
      Biochemistry
      Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE