Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1998-03-25
2000-05-09
Mertz, Prema
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 72, 435 721, 435325, 435372, 4353723, 435375, 530351, C07K 1452, G01N 3353
Patent
active
060602589
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a novel neutrophil chemotactic lymphokine and a diagnostic agent for diagnosing an attack of drug-induced granulocytopenia comprising this lymphokine.
BACKGROUND ART
Granulocytopenia refers to a condition that the number of granulocytes in peripheral blood is decreased, and is a concept including agranulocytosis marked by severe decrease or loss in granulocytes and accompanied by a grave condition. Of these, the agranulocytosis has a high mortality due to infectious diseases.
As causes of the granulocytopenia, have been known the attack attending on other various diseases, administration of a drug, and the like. Of these, the granulocytopenia caused by the drug includes drug-induced granulocytopenia. The attack of the drug-induced granulocytopenia cannot be predicted prior to the administration of the drug under the circumstances. Further, no drug for treating the drug-induced granulocytopenia after the attack has been known, and so its treatment only depends on stopping the administration of a causative drug under the circumstances.
Accordingly, it is an object of the present invention to provide a diagnostic agent capable of predicting an attack of drug-induced granulocytopenia.
DISCLOSURE OF THE INVENTION
In view of the foregoing circumstances, the present inventors have paid attention to granulocyte chemotactic factors, particularly, neutrophil chemotactic lymphokines and carried out a varied investigation as to their diversity and specificity. As a result, it has been found that a plurality of subspecies different in isoelectric point from one other exist in the neutrophil chemotactic lymphokines. The inventors have succeeded in isolating a novel lymphokine not reported heretofore therefrom. It has also been found that there is a correlation between the chemotaxis of a neutrophil by such a novel lymphokine and the attack of drug-induced granulocytopenia, namely, an individual having a neutrophil low in chemotactic capability to the lymphokine is attacked by drug-induced granulocytopenia, and that the same correlation as described above is also present in a GM-CSF (granulocyte-macrophage colony-stimulating factor), thus leading to completion of the present invention.
According to the present invention, there are thus provided a neutrophil chemotactic lymphokine having an isoelectric point at 6.8-7.0 and a cell line which produces such a lymphokine.
According to the present invention, there are also provided an agent and a kit for diagnosing drug-induced granulocytopenia, which comprises the lymphokine described above.
According to the present invention, there are further provided an agent and a kit for diagnosing drug-induced granulocytopenia, which comprises a GM-CSF.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 diagrammatically illustrates a relationship between isoelectric focusing fractions of CFR-24 culture solution and neutrophil chemotactic activity,
FIG. 2 diagrammatically illustrates relationships between chemotaxis indices (CI) of a neutrophil to NCL-4 and GM-CSF and specimens, and
FIG. 3 diagrammatically illustrates relationships between expression rates of CD11b in a neutrophil by NCL-4 and GM-CSF and specimens.
BEST MODE FOR CARRYING OUT THE INVENTION
The neutrophil chemotactic lymphokine (hereinafter referred to as NCL-4) having an isoelectric point at 6.8-7.0 according to the present invention can be obtained from a T cell line obtained by transforming, for example, a normal T cell with a virus.
Here, the NCL-4 producing T cell line can be obtained by coculturing, for example, a normal human mononuclear leukocyte together with a human adult T cell leukemia cell line (for example, MT2) and establishing a T cell line transformed with a virus produced by the leukemia cell line.
In order to collect NCL-4 from this virus-transformed T cell line, it is only necessary to culture this cell line, conduct isoelectric focusing of the culture solution thereof using neutrophil chemotactic capability as an index and collect a fraction having an iso
REFERENCES:
patent: 5679356 (1997-10-01), Bonnem et al.
Japanese Journal of Allergology, "Allergy", vol. 44, No. 8,Aug. 1995 (with English translation).
The Abstract #665, Volume for the Ninth International Congress of Immunology, Jul. 1995, San Francisco, CA Nishi Yama et al.
International Search Report.
Mertz Prema
Otsuka Pharmaceutical Co. Ltd.
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