Sulphostin, a Novel Inhibitor of Dipeptidyl Peptidases IV (DPPIV) That Stimulates Hematopoiesis in Mice

CD26, a membrane-bound ectopeptidase, is known as an activated T cell marker with dipeptidyl peptidase IV (DPPIV) activity that has diverse functional roles in the regulation of peptide hormones, neuropeptides, chemokines and growth factors. We recently isolated a novel inhibitor of DPPIV, sulphosti...

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Veröffentlicht in:Journal of antibiotics 2005-02, Vol.58 (2), p.111-117
Hauptverfasser: Abe, Masatoshi, Abe, Fuminori, Nishimura, Chihiro, Ichimura, Eiji, Ogasawara, Asuka, Ichinei, Megumi, Muraoka, Yasuhiko, Saino, Tetsushi
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Sprache:eng
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Zusammenfassung:CD26, a membrane-bound ectopeptidase, is known as an activated T cell marker with dipeptidyl peptidase IV (DPPIV) activity that has diverse functional roles in the regulation of peptide hormones, neuropeptides, chemokines and growth factors. We recently isolated a novel inhibitor of DPPIV, sulphostin, from culture broth of Streptomyces sp. MK251-43F3. We investigated herein the hematopoietic effect of sulphostin in mice and found that sulphostin induced the production of granulocyte colony-stimulating factor (G-CSF), stimulated myeloblasts in bone marrow, and increased neutrophil numbers in peripheral blood in both normal mice and mice with cyclophosphamide-induced leucopenia. Sulphostin desulfonate, in addition to sulphostin, has a similar inhibitory effect on DPPIV and stimulatory effect on neutrophils. These results suggest that DPPIV/CD26 might be a novel target for hematopoietic stimulation and DPPIV inhibitors including sulphostin and derivatives may be candidates for further development.
ISSN:0021-8820
1881-1469
DOI:10.1038/ja.2005.14