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Biotech / Medical : XOMA. Bull or Bear? -- Ignore unavailable to you. Want to Upgrade?

To: aknahow who wrote (7543)	10/26/1998 10:27:00 PM
From: Bluegreen	Respond to of 17367

George, remember what I was saying about the totally different environments of spinal fluid and "complex environment of human blood" as portrayed in last sentence of this abstract. George, why have an emergency room when you know the longer it takes to treat a patient in dire straits, the worse the outcome? Why have ambulances?<g> Now, doesn't Xoma have some LBP patents and don't some of these cover a LBP that doesn't kick on CD14? A Synthetic Lipopolysaccharide-Binding Peptide Based on Amino Acids 2739 of Serum Amyloid P Component Inhibits Lipopolysaccharide-Induced Responses in Human Blood Carla J. C. de Haas,1 Marijke E. van der Tol, Kok P. M. Van Kessel, Jan Verhoef, and Jos A. G. Van Strijp Eijkman Winkler Institute, Department of Inflammation, Utrecht, The Netherlands The Journal of Immunology, 1998, 161: 3607-3615. LPS-binding proteins in plasma play an important role in modifying LPS toxicity. Significant properties have already been attributed to the LPS-binding protein (LBP). It accelerates LPS toxicity as well as incorporation into high-density lipoproteins, leading to neutralization of LPS in serum. A search for other LPS-binding components in serum, using LPS-coated magnetic beads, revealed a new LPS-binding protein. N-terminal microsequencing identified this protein as serum amyloid P component (SAP). Purified SAP bound to smooth and rough types of LPS via the lipid A part. SAP inhibited the binding of FITC-labeled ReLPS (LPS from Salmonella minnesota strain R595) to human monocytes and the ReLPS-induced priming of the oxidative burst of human neutrophils only in the presence of low concentrations of LBP. In search for the LPS binding site of SAP, we found that pep2739, a 13-mer peptide consisting of amino acids 2739 of SAP, competitively inhibited the binding of LPS to SAP. In addition, pep2739 significantly inhibited ReLPS-induced responses in phagocytes in the presence of serum, as well as in human whole blood. Carboxamidomethylated pep2739 showed an even more pronounced reduction of the ReLPS-induced priming of phagocytes in human blood. Performing gel filtration of FITC-labeled ReLPS incubated with soluble CD14, we showed that SAP could not prevent binding of LPS to soluble CD14, in contrast to pep2739. The ability of pep2739 to antagonize specifically the effects of LPS in the complex environment of human blood suggests that pep2739 may be a novel therapeutic agent in the treatment of Gram-negative sepsis.