title: The tissue inhibitor of metalloproteinases-1 improves migration and adhesion of hematopoietic stem and progenitor cells.
abstract: Homing and engraftment of hematopoietic stem and progenitor cells (HSPCs) during bone marrow transplantation are critically dependent on integrins such as β1-integrin. In the present study, we show that β1-integrin and the tetraspanin CD63 form a cell surface receptor complex for the soluble serum protein tissue inhibitor of metalloproteinases-1 (TIMP-1) on human CD34⁺ HSPCs. Through binding to this receptor complex, TIMP-1 activates β1-integrin, increases adhesion and migration of human CD34⁺ cells, and protects these cells from induced apoptosis. TIMP-1 stimulation in murine bone marrow mononuclear cells also promotes migration and adhesion; this is associated with augmented homing of murine mononuclear cells and of murine LSK⁺ cells during bone marrow transplantation. These results not only indicate that TIMP-1 is conducive to HSPC homing; they also identify CD63 and β1-integrin as a TIMP-1 receptor complex on HSPCs.
authors: Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany. matthias.wilk@med.uni-duesseldorf.de
authors: C Matthias
authors: CM
authors: Wilk
authors: Frank A
authors: FA
authors: Schildberg
authors: Marcel A
authors: MA
authors: Lauterbach
authors: Ron-Patrick
authors: RP
authors: Cadeddu
authors: Julia
authors: J
authors: Fröbel
authors: Volker
authors: V
authors: Westphal
authors: René H
authors: RH
authors: Tolba
authors: Stefan W
authors: SW
authors: Hell
authors: Akos
authors: A
authors: Czibere
authors: Ingmar
authors: I
authors: Bruns
authors: Rainer
authors: R
authors: Haas
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D002465:Cell Movement; D005260:Female; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D051379:Mice; D060149:Tetraspanin 30 / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: C554586:CD63 protein, human; C554587:Cd63 protein, mouse; D019012:Integrin beta1; C560822:TIMP1 protein, human; D060149:Tetraspanin 30; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1