CD26 inhibition and hematopoiesis: a novel approach to enhance transplantation.
Dipeptidylpeptidase IV/CD26 is expressed on the surface of various cell types. Through its enzymatic activity, its major function is to cleave the N-terminal dipeptide from diverse molecules including members of the chemokine family of cytokines. The N-terminus of these chemokines is important for activation of and binding to seven-transmembrane G-protein linked chemokine receptors, and early studies showed truncation by CD26 physiologically alters these properties of select chemokines resulting in diverse functional outcomes. Stromal-derived factor-1 (SDF-1/CXCL12), a chemokine involved in hematopoietic cell chemotaxis, homing, mobilization and survival, is cleaved by CD26 producing a form that is inactive in CXCR4 signaling and has some antagonistic properties in vitro. Recent studies have shown that the inhibition of cell-surface CD26 peptidase activity on hematopoietic stem/progenitor cell (HSC/HPC) populations increases their SDF-1/CXCL12 directed chemotaxis in vitro, and in vivo homing and engraftment. CD26 inhibition may, therefore, represent a novel approach to increasing the efficacy and success of HSC/HPC transplantation, especially under conditions of limiting donor cell yield.
Campbell
Timothy B
TB
Department of Microbiology and Immunology, and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Broxmeyer
Hal E
HE
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D017690:Cell Transplantation; D054407:Chemokine CCL4 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis* / Q000096:biosynthesis*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D054367:Receptors, CXCR3 / Q000378:metabolism; D015398:Signal Transduction; D016896:Treatment Outcome
D018952:Antigens, CD34; C496535:Ccl4 protein, mouse; D054407:Chemokine CCL4; D018925:Chemokines; C515188:Cxcr3 protein, mouse; D008024:Ligands; D054367:Receptors, CXCR3; D018819:Dipeptidyl Peptidase 4