sulphostin and Leukopenia

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.

Topics: Alkylating Agents; Animals; Bone Marrow Cells; Cyclophosphamide; Cytokines; Dipeptidyl Peptidase 4; Enzyme-Linked Immunosorbent Assay; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Leukocyte Count; Leukopenia; Male; Mice; Mice, Inbred ICR; Neutrophils; Organophosphorus Compounds; Piperidones; Protease Inhibitors; Stimulation, Chemical