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Effects of a novel purine nucleoside phosphorylase inhibitor, BCX-34, on activation and proliferation of normal human lymphoid cells.
- Source :
-
Immunopharmacology [Immunopharmacology] 1998 Jul; Vol. 40 (1), pp. 1-9. - Publication Year :
- 1998
-
Abstract
- The antiproliferative effect of BCX-34 was tested in normal human peripheral blood mononuclear cells (PBMCs) induced to proliferate with OKT3, tetanus toxoid, the mixed lymphocyte reaction, or IL-2. In the case of OKT3, tetanus toxoid, or the MLR the IC50s ranged between 0.7 and 4 microM. With IL-2, the IC50 was 14.6 microM. In T-cells purified by rosetting the IC50 with IL-2 was 0.62 microM. In CD4 or CD8 cells obtained by magnetic activated cell sorting the IC50s with IL-2 were 0.24 and 0.62 microM, respectively. BCX-34 inhibition of proliferation in human PBMCs may not depend entirely upon the accumulation of intracellular dGTP because tetanus toxoid-induced proliferation was inhibited in the absence of deoxyguanosine and was not reversed by deoxycytidine. BCX-34 did not inhibit IL-2 release from PBMCs and did not alter PBMC viability. The results of these studies show that BCX-34 is a potent inhibitor of normal human T-cell proliferation induced by antigenic or IL-2 stimulation. BCX-34 in normal human T-cells has a deoxyguanosine-independent mechanism to suppress in vitro proliferation. BCX-34 appears to have little effect on T-cell viability. The data suggest that BCX-34 may be useful in the treatment of T-cell proliferative disorders.
- Subjects :
- Cell Division drug effects
Cell Survival drug effects
Dose-Response Relationship, Drug
Guanine pharmacology
Humans
Interleukin-2 metabolism
Interleukin-2 pharmacology
Lymphocyte Activation drug effects
Lymphocyte Culture Test, Mixed
Muromonab-CD3 pharmacology
T-Lymphocytes immunology
Tetanus Toxin pharmacology
Enzyme Inhibitors pharmacology
Guanine analogs & derivatives
Immunosuppressive Agents pharmacology
Purine-Nucleoside Phosphorylase antagonists & inhibitors
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0162-3109
- Volume :
- 40
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 9776473
- Full Text :
- https://doi.org/10.1016/s0162-3109(98)00012-5