Serum albumin strongly influences SDF-1 dependent migration.
Stem cell migration is largely regulated by the chemokine SDF-1 and its receptor CXCR4. In the present study, we analyzed the effect of protein on SDF-1 dependent chemotaxis using CXCR4 expressing primary CD34+ hematopoietic progenitor cells for transwell migration assays. We show that migration towards SDF-1 is abolished in the absence of protein, while addition of serum albumin rescues SDF-1 dependent migration. Acid hydrolyzation or tryptic digest of protein eliminates its migration supporting effect, showing that the intact protein is necessary. We demonstrate that gradients of human serum albumin (HSA) that are physiologically present in vivo between human plasma and interstitial fluid (bone marrow) greatly influence SDF-1 dependent migration of hematopoietic progenitor cells. While SDF-1 dependent migration is strongly enhanced in the presence of a HSA gradient from 4% (plasma) towards 1% (interstitial fluid), reversion of the protein concentrations inhibits SDF-1 dependent chemotaxis. Furthermore, migration is induced to lower serum albumin concentrations in the presence of equal SDF-1 concentration, while albumin gradients in the absence of SDF-1 have no effect. Our results suggest that physiological gradients of serum albumin between blood and bone marrow support SDF-1 dependent homing of hematopoietic progenitor cells to the stem cell niche.
Ryser
Martin F
MF
Department of Pediatrics, University Clinic Carl Gustav Carus, Dresden, Germany.|DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden, Technical University Dresden, Dresden, Germany.
Thieme
Sebastian
S
Department of Pediatrics, University Clinic Carl Gustav Carus, Dresden, Germany.|DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden, Technical University Dresden, Dresden, Germany.
Bornhäuser
Martin
M
Medical Clinic I, University Clinic Carl Gustav Carus, Dresden, Germany.|DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden, Technical University Dresden, Dresden, Germany.
Lehmann
Romy
R
Department of Pediatrics, University Clinic Carl Gustav Carus, Dresden, Germany.
Brenner
Sebastian
S
Department of Pediatrics, University Clinic Carl Gustav Carus, Dresden, Germany. sebastian.brenner@uniklinikum-dresden.de.|DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden, Technical University Dresden, Dresden, Germany. sebastian.brenner@uniklinikum-dresden.de.|Department of Pediatrics Bldg. 21, University Clinic Dresden, Fetscherstr. 74, 01307, Dresden, Germany. sebastian.brenner@uniklinikum-dresden.de.
D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008970:Molecular Weight; D010766:Phosphorylation / Q000187:drug effects; D012709:Serum Albumin / Q000494:pharmacology*
D054377:Chemokine CXCL12; D017077:Culture Media, Conditioned; D012709:Serum Albumin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3