Characterization of bone marrow laminins and identification of alpha5-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-1 (alpha1beta1gamma1), 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 alpha1 chain but rather laminin alpha2, alpha4, and alpha5 polypeptides were found in bone marrow. Our data suggest presence of laminin-2 (alpha2beta1gamma1), laminin-8 (alpha4beta1gamma1), and laminin-10 (alpha5beta1gamma1) in bone marrow. Northern blot analysis showed expression of laminin alpha1, alpha2, alpha4, and alpha5 chains in long-term bone marrow cultures, indicating upregulation of laminin alpha1 chain expression in vitro. Laminins containing alpha5 chain, in contrast to laminin-1, were strongly adhesive for multipotent hematopoietic FDCP-mix cells. Integrin alpha6 and beta1 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.
Gu
Y
Y
Department of Animal Physiology, Biomedical Center, Uppsala, Sweden; the Department of Experimental Medicine, University of Erlangen, Erlangen, Germany.
Sorokin
L
L
Durbeej
M
M
Hjalt
T
T
Jönsson
J I
JI
Ekblom
M
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D005269:Femur; D006801:Humans; D015151:Immunoblotting; D007797:Laminin / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D051379:Mice; D008810:Mice, Inbred C57BL; D013977:Tibia
D007797:Laminin; C097043:laminin alpha5