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Your search keyword '"Kiyoi T"' showing total 2 results
Start Over Author "Kiyoi T" Journal thrombosis and haemostasis
2 results on '"Kiyoi T"'

1. Anti-alphavbeta3 antibodies in chronic immune thrombocytopenic purpura

Author

Kosugi S, Yoshiaki Tomiyama, Honda S, Kashiwagi H, Shiraga M, Tadokoro S, Kiyoi T, Kurata Y, and Matsuzawa Y

Subjects
Blood Platelets, Male, Purpura, Thrombocytopenic, Idiopathic, Umbilical Veins, Platelet Count, Enzyme-Linked Immunosorbent Assay, Platelet Glycoprotein GPIIb-IIIa Complex, Cross Reactions, Cytotoxicity Tests, Immunologic, Humans, Female, Receptors, Vitronectin, Endothelium, Vascular, Autoantibodies
Abstract

In chronic immune thrombocytopenic purpura (ITP), anti-GPIIb-IIIa (alphaIIbbeta3) autoantibodies have been detected in serum and/or platelet-associated IgG (PAIgG) and considered as one of the major causes. We examined whether anti-alphavbeta3 antibodies might be present in ITP cases because of the similarity between alphavbeta3 and GPIIb-IIIa (alphaIIbbeta3). Modified antigen capture ELISA (MACE) using human umbilical vein endothelial cells (HUVEC) showed the presence of serum anti-alphavbeta3 antibodies in 23 of 80 ITP patients (29%). Cross-adsorption studies between platelets and HUVEC demonstrated that most of anti-alphavbeta3 and anti-GPIIb-IIIa antibodies exclusively reacted with alphavbeta3 and GPIIb-IIIa, respectively. Platelet-associated anti-GPIIb-IIIa antibodies did not react with alphavbeta3, either. Interestingly, patients having anti-alphavbeta3 antibodies showed significantly lower platelet counts than negative patients. These results indicate the serum anti-alphavbeta3 antibodies are different ones from the classical anti-GPIIb-IIIa (alphaIIbbeta3) antibodies and would provide a new insight into the pathophysiology of ITP as well as the autoantigenic epitopes on beta3 integrins.

Published
2001

2. Amino acid mutagenesis within ligand-binding loops in alpha v confers loss-of-function or gain-of-function phenotype on integrin alpha v beta 3.

Author

Honda S, Kashiwagi H, Kiyoi T, Kato H, Kosugi S, Shiraga M, Kurata Y, and Tomiyama Y

Subjects
Animals, Binding Sites, Fibrinogen metabolism, Immunoglobulin Fab Fragments metabolism, Integrin alphaV chemistry, Integrin alphaVbeta3 chemistry, Integrin alphaVbeta3 genetics, Mice, Mutagenesis, Phenotype, Protein Binding, Amino Acid Substitution, Integrin alphaV genetics, Integrin alphaVbeta3 metabolism
Abstract

The crystal structure of alpha(v)beta(3) in complex with a cyclic RGD-containing ligand has recently been demonstrated. However, the functional significance of each residue within ligand binding loops has not been fully elucidated. Here, by employing alanine-scanning mutagenesis, we have examined the functional role of ligand contact residues in alpha(v). Tyr178 --> Ala substitution (Tyr178Ala) and Asp218Ala abolished a monovalent ligand, WOW-1 Fab binding as well as soluble fibrinogen binding, which is in perfect agreement with the crystallography. However, Asp150Ala showed no or only a modest inhibition of ligand binding. In contrast, Tyr substitution at Ala215 (Ala215Tyr) increased WOW-1 Fab binding, suggesting that the substitution increased the integrin affinity. The adhesion assay to immobilized fibrinogen showed essentially the same data as obtained using soluble ligands. Our present data indicate that Tyr178 and Asp218, but not Asp150 in alpha(v) is critically involved in ligand-binding and that Ala215 could regulate the affinity of alpha(v)beta(3).

Published
2004
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