HEMATOPOIESIS Characterization of Bone Marrow Laminins and Identification of a5-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 a, b, and g polypeptides. So far five a, three b, and two g 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-1 (a1b1g1), 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 a1 chain but rather laminin a2, a4, and a5 polypeptides were found in bone marrow. Our data suggest presence of laminin-2 (a2b1g1), laminin-8 (a4b1g1), and laminin-10 (a5b1g1) in bone marrow. Northern blot analysis showed expression of laminin a1, a2, a4, and a5 chains in long-term bone marrow cultures, indicating upregulation of laminin a1 chain expression in vitro. Laminins containing a5 chain, in contrast to laminin-1, were strongly adhesive for multipotent hematopoietic FDCPmix cells. Integrin a6 and b1 chains mediated this adhesion, as shown by antibody perturbation experiments. Our findings indicate that laminins other than laminin-1 are functional in adhesive interactions in bone marrow. r 1999 by The American Society of Hematology.