Characterization of bone marrow laminins and identification of α5-containing laminins as adhesive proteins for multipotent hematopoietic FDCP-mix cells

Laminins are extracellular matrix glycoproteins that influence the phenotype and functions of many types of cells. Laminins are heterotrimers composed of alpha, beta, and gamma polypeptides. So far five alpha, three beta, and two gamma polypeptide chains, and 11 variants of laminins have been proposed. Laminins interact in vitro with mature blood cells and malignant hematopoietic cells. Most studies have been performed with laminin-l (alpha 1 beta 1 gamma 1), and its expression in bone marrow is unclear. Employing an antiserum reacting with most laminin isoforms, we found laminins widely expressed in mouse bone marrow. However, no laminin alpha 1 chain but rather laminin alpha 2, alpha 4, and alpha 5 polypeptides were found in bone marrow. Our data suggest presence of laminin-2 (alpha 2 beta 1 gamma 1), laminin-l (alpha 4 beta 1 gamma 1). and laminin-10 (alpha 5 beta 1 gamma 1) in bone marrow. Northern blot analysis showed expression of laminin alpha 1, alpha 2, alpha 4, and alpha 5 chains in long-term bone marrow cultures, indicating upregulation of laminin alpha 1 chain expression in vitro. Laminins containing alpha 5 chain, in contrast to laminin-l, were strongly adhesive for multipotent hematopoietic FDCP-mix cells. Integrin alpha 6 and beta 1 chains mediated this adhesion, as shown by antibody perturbation experiments. Our findings indicate that laminins other than laminin-l are functional in adhesive interactions in bone marrow. (C) 1999 by The American Society of Hematology.