Inhibition of L-selectin and P-selectin mediated binding using heparin
AssigneeThe Regents of the University of California
InventorsAjit Varki, Andrea Koenig
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Abstract
The present invention provides methods of inhibiting L-selectin and P-selectin mediated binding in a subject by administering heparin to the subject in an amount that does not produce substantial anticoagulant activity or undesirable bleeding in the subject. In addition, the invention provides methods of treating a subject having a pathology characterized, at least in part, by abnormal L-selectin or P-selectin mediated binding by administering heparin to the subject in an amount that results in attaining a concentration of less than about 0.2-0.4 units heparin per ml of plasma in the subject.
Claims28
A method for screening heparin for inhibiting binding of one or more selectins selected from the group consisting of L-selectin and P-selectin to a selectin ligand, said method comprising:
- a) providing:
- i) one or more selectins selected from the group consisting of L-selectin and P-selectin;
- ii) a ligand for one or more selectins selected from the group consisting of L-selectin and P-selectin;
- and
- iii) heparin;
- b) contacting said one or more selectins and said ligand in the presence and absence of said heparin;
- and
- c) detecting a reduced level of binding of said one or more selectins to said ligand in the presence of said heparin compared to in the absence of said heparin, wherein:
- i) said reduced level of binding is detected using a concentration of said heparin that is lower than the concentration of heparin that produces one or more activities selected from the group consisting of anticoagulant activity in vivo and undesirable bleeding in vivo;
- and
- ii) said concentration of said heparin does not reduce the level of binding of E-selectin to a E-selectin ligand.
A method for screening heparin for inhibiting binding of P-selectin to a P-selectin ligand, said method comprising:
- a) providing:
- i) P-selectin;
- ii) a P-selectin ligand;
- and
- iii) heparin;
- b) contacting said P-selectin and said P-selectin ligand in the presence and absence of said heparin;
- and
- c) detecting a reduced level of binding of said P-selectin to said P-selectin ligand in the presence of said heparin compared to in the absence of said heparin, wherein:
- i) said reduced level of binding is detected using a concentration of said heparin that is lower than the concentration of heparin that produces one or more activities selected from the group consisting of anticoagulant activity in vivo and undesirable bleeding in vivo;
- ii) said concentration of said heparin does not reduce the level of binding of E-selectin to a E-selectin ligand;
- and
- iii) said concentration of said heparin does not reduce the level of binding of L-selectin to a L-selectin ligand.
A method for screening heparin for inhibiting binding of L-selectin to a L-selectin ligand, said method comprising:
- a) providing:
- i) L-selectin;
- ii) a L-selectin ligand;
- and
- iii) heparin;
- b) contacting said L-selectin and said L-selectin ligand in the presence and absence of said heparin;
- and
- c) detecting a reduced level of binding of said L-selectin to said L-selectin ligand in the presence of said heparin compared to in the absence of said heparin, wherein:
- i) said reduced level of binding is detected using a concentration of said heparin that is lower than the concentration of heparin that produces one or more activities selected from the group consisting of anticoagulant activity in vivo and undesirable bleeding in vivo;
- ii) said concentration of said heparin does not reduce the level of binding of E-selectin to a E-selectin ligand;
- and
- iii) said concentration of said heparin does not reduce the level of binding of P-selectin to a P-selectin ligand.
Dependencies are inferred from the claim text.