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, 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.
Abe
Masatoshi
M
R. & D. Division, Nippon Kayaku Co. Ltd., 31-12 Shimo 3-chome, Kita-ku, Tokyo 115-8588, Japan.
Abe
Fuminori
F
Nishimura
Chihiro
C
Ichimura
Eiji
E
Ogasawara
Asuka
A
Ichinei
Megumi
M
Muraoka
Yasuhiko
Y
Saino
Tetsushi
T
D000477:Alkylating Agents; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D003520:Cyclophosphamide; D016207:Cytokines / Q000096:biosynthesis; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D006410:Hematopoiesis / Q000187:drug effects*; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010881:Piperidones / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000477:Alkylating Agents; D016207:Cytokines; D009943:Organophosphorus Compounds; D010881:Piperidones; D011480:Protease Inhibitors; C440633:sulphostin; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D018819:Dipeptidyl Peptidase 4