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001-es BibID:BIBFORM034925
Első szerző:Deckmyn, Hans
Cím:An echistatin-like Arg-Gly-Asp (RGD)-containing sequence in the heavy chain CDR3 of a murine monoclonal antibody that inhibits human platelet glycoprotein IIb/IIIa function / Deckmyn H., Stanssens P., Hoet B., Declerck P. J., Lauwereys M., Gansemans Y., Tornai I., Vermylen J.
Dátum:1994
ISSN:0007-1048
Megjegyzések:We describe the production and biochemical characterization of the first GPIIb/IIIa-inhibiting monoclonal antibody that contains an RGD sequence in the CDR3 region of the heavy chain. Monoclonal antibodies obtained by immunizing mice with human platelets were screened using consecutive ELISAs based on human platelets and immuno-affinity-purified glycoprotein (GP) IIb/IIIa coated on microtitre plates. Out of 30 monoclonal antibodies reacting with GPIIb/IIIa, one, MA-16N7C2, potently inhibited platelet aggregation induced by ADP, thrombin, arachidonic acid, collagen, U46619, adrenaline and platelet-activating factor, whereas ristocetin-induced aggregation was unaffected. MA-16N7C2 (IgG2a) bound approximately 4 times faster to activated than to resting platelets, with a Kdcalc of 6.6nM and of 17.5nM, respectively. Equilibrium binding studies to non-activated platelets showed a Kd of 18.2nM with 41 x 10(3) binding sites per platelet. The antibody recognized GPIIb/IIIa only as a Ca(2+)-dependent complex. MA-16N7C2 blocked fibrinogen and von Willebrand factor binding to GPIIb/IIIa in a competitive manner with a Ki of 8.5nM and 13.2nM, respectively. Sequence analysis revealed a RGD-containing sequence with homology to disintegrins, in the CDR3 region of the heavy chain. That this RGD-containing sequence could be involved in the interaction of the antibody to GPIIb/IIIa was finally indicated by showing that the binding is completely and competitively inhibited by echistatin.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
antiplatelet
disintegrin
integrin
antibody sequence
külföldön készült közlemény
Megjelenés:British Journal Of Haematology. - 87 : 3 (1994), p. 562-571. -
További szerzők:Stanssens, Patrick Hoet, Bernard Declerck, Paul J. Lauwereys, Marc Gansemans, Yannick Tornai István (1954-) (belgyógyász, gasztroenterológus) Vermylen, Jozef
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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