Function of fibrinogen gamma-chain dodecapeptide-conjugated latex beads under flow.
In order to perform a fundamental study of platelet substitutes, novel particles that bound to activated platelets were prepared using two oligopeptides conjugated to latex beads. The oligopeptides were CHHLGGAKQAGDV (H12), which is a fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411), and CGGRGDF (RGD), which contains a fibrinogen alpha-chain sequence (alpha 95-98 RGDF). Both peptides contained an additional amino-terminal cysteine to enable conjugation. Human serum albumin was adsorbed onto the surface of latex beads (average diameter 1microm) and pyridyldisulfide groups were chemically introduced into the adsorbed protein. H12 or RGD peptides were then chemically linked to the modified surface protein via disulfide linkages. H12- or RGD-conjugated latex beads prepared in this way enhanced the in vitro thrombus formation of activated platelets on collagen-immobilized plates under flowing thrombocytopenic-imitation blood. Based on the result of flow cytometric analyses of agglutination, PAC-1 binding, antiP-selectin antibody binding, and annexin V binding, the H12-conjugated latex beads showed minimal interaction with non-activated platelets. These results indicate the excellent potential of H12-conjugated particles as a candidate for a platelet substitute.
Takeoka
Shinji
S
Advanced Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555, Japan.
Okamura
Yosuke
Y
Teramura
Yuji
Y
Watanabe
Naohide
N
Suzuki
Hidenori
H
Tsuchida
Eishun
E
Handa
Makoto
M
Ikeda
Yasuo
Y
D040761:Biomimetic Materials / Q000378:metabolism; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology*; D001802:Blood Substitutes / Q000378:metabolism*; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D005434:Flow Cytometry; D018056:Hemorheology / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D046911:Macromolecular Substances; D008863:Microspheres; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology*; D017713:Platelet Transfusion / Q000295:instrumentation / Q000379:methods*; D013921:Thrombocytopenia / Q000378:metabolism*
D001802:Blood Substitutes; D020099:Coated Materials, Biocompatible; D046911:Macromolecular Substances; D009842:Oligopeptides; D005340:Fibrinogen