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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-03-0796.

Submitted March 13, 2002
Accepted September 5, 2002
Laminin isoform-specific promotion of adhesion and migration of human bone marrow progenitor cells
Yu-Chen Gu, Jarkko Kortesmaa, Karl Tryggvason, Jenny Persson, Peter Ekblom, Sten-Eirik Jacobsen, and Marja Ekblom*
Department of Cell and Molecular Biology, Lund University, Lund, Sweden
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Department of Laboratory Medicine, Lund University, Lund, Sweden; Stem Cell Laboratory, Lund University, Lund, Sweden
Department of Laboratory Medicine, Lund University, Lund, Sweden
* Corresponding author; email: marja.ekblom{at}medkem.lu.se.
Laminins are ß heterotrimeric extracellular proteins, which regulate cellular functions by adhesion to integrin and non-integrin receptors. Laminins containing 4 and 5 chains are expressed in bone marrow but their interactions with hematopoietic progenitors are unknown. We studied human bone marrow cell adhesion to laminin-10/11 ( 5ß1 1/ 5ß2 1), laminin-8 ( 4ß1 1), laminin-1 ( 1ß1 1 and fibronectin. 35-40% of CD34+ and CD34+CD38- stem and progenitor cells adhered to laminin-10/11 and 45-50% adhered to fibronectin, whereas they adhered less to laminin-8 and to laminin-1. Adhesion of CD34+CD38- cells to laminin-10/11 was maximal without integrin activation, whereas adhesion to other proteins was dependent on protein kinase C activation by TPA. FACS analysis showed expression of integrin 6 chain on the majority of CD 34+ and CD34+CD38- cells. Integrin 6 and ß1 chains were involved in binding of both cell fractions to laminin-10/11 and laminin-8. Laminin-10/11 was highly adhesive to lineage committed myelomonocytic and erythroid progenitor cells, and most lymphoid and myeloid cell lines studied, whereas laminin-8 was less adhesive. In functional assays, both laminin-8 and laminin-10/11 facilitated SDF-1 stimulated transmigration of CD34+ cells, by an integrin 6 receptor mediated mechanism. In conclusion, we demonstrate laminin isoform specific adhesive interactions with human bone marrow stem, progenitor and more differentiated cells. The cell-adhesive laminins affected migration of hematopoietic progenitors, suggesting a physiological role for laminins during hematopoiesis.

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