Characterization of bone marrow laminins and identification of alpha5-containing laminins as adhesive proteins for multipotent hematopoietic FDCP-Mix cells

Gu Y., Sorokin L., Durbeej M., Hjalt T., Jonsson J.I., Ekblom M.
Blood, 1999

Laminins interact in vitro with mature blood cells and malignant hematopoietic cells. Here they show that laminins are widely expressed in mouse bone marrow. Laminin a2, a4, and a5 polypeptides were found suggesting presence of laminin-211, laminin-411, and laminin-511 in bone marrow. Gene expression of laminin a1, a2, a4, and a5 chains in long-term bone marrow cultures, indicating up-regulation of laminin a1 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.


Characterization and functional analysis of laminin isoforms in human bone marrow

Siler U., Seiffert M., Puch S., Richards A., Torok-Storb B., Müller C.A, Sorokin L., Klein G.
Blood, 2000

Based on gene expression, laminin-411/421 and laminin-511/521 are the most abundant laminin isoforms synthesized by human bone marrow stromal cells. Laminin-511/521 preparations showed strong adhesive interactions with human CD34+ cell lines. Antibodies against the B1 integrin subunit inhibited these interactions. In addition to its adhesion-mediating properties, laminin-511/521 preparations also showed a mitogenic activity for human hematopoietic progenitor cells. Other laminin isoforms tested, especially laminin-111 and laminin-211 and 221, showed only weak or no adhesive interactions with the hematopoietic cell lines tested and are suggested to play a minor role in the hematopoietic microenvironment. In the bone marrow, LN‐511 and 521 are the major laminins and show strongly adhesive and mitogenic activities toward early developing HSCs.


Contribution of α6 integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with α4 integrins

Qian H., Tryggvason K., Jacobsen S.E., Ekblom M.
Blood, 2006

Integrin a6 chain is ubiquitously expressed in human and mouse hematopoietic stem and progenitor cells. Integrin a6 chain is ubiquitously expressed in human HPCs. Laminin-411 and -511, are present in subendothelial basement membranes of sinusoids in bone marrow, at sites of hematopoietic cell development and trafficking and might therefore regulate HSC functions. In this paper they show that mouse HSC and progenitors express a6B1 integrin which mediates high cell adhesion to laminin-511 and 521 and to laminin-411 to a lower extent. Blocking of a6 significantly reduced progenitor cell homing to bone marrow in mice. Integrin a4 receptors are also important for homing of HSCs to bone marrow (but not to spleen). The first data showing that a6 integrins (LN521/511 binding) function in vivo as hematopoietic stem and progenitor cell homing receptors. Also show the role of integrin a4 receptor for homing of long-term multilineage reconstituting HSCs and collaboration of these 2 integrins in homing of short-term HSCs.


Laminin isoform–specific promotion of adhesion and migration of human bone marrow progenitor cells

Gu Y-C., Kortesmaa J., Tryggvason K., Persson J., Ekblom P., Jacobsen S-E., Ekblom M.

Here they studied human bone marrow cell adhesion to laminin-511/521, laminin-411, laminin-111, and fibronectin. About 35% to 40% of CD34+ and CD34+CD38- stem and progenitor cells adhered to laminin-511/521, and 45% to 50% adhered to fibronectin, whereas they adhered less to laminin-411 and laminin-111. Adhesion of CD34+CD38- cells to laminin-511/521 was maximal without integrin activation, whereas adhesion to other proteins was dependent on protein kinase C activation. Integrin a6 chain expressed on most CD34+ and CD34+CD38-cells. Laminin-511/521 was highly adhesive to lineage-committed myelomonocytic and erythroid progenitor cells and most lymphoid and myeloid cell lines studied, whereas fibronectin and laminin-411 was less adhesive. Laminin-511/521was a ubiquitous adhesive protein for differentiated precursors of both B-lymphocytic, erythroid, megakaryocytic, and myelomonocytic cell lineages, whereas adhesion to laminin-411 and laminin-111 was restricted to a few cell lines. CD34+ cell migration was greatly enhanced through membranes coated with Laminin-511/521 and laminin-411. Our findings raise the possibility that a4 and a5 laminins are involved in mobilization and homing of hematopoietic progenitor cells.


Laminin expression during bone marrow mononuclear cell transplantation in hepatectomized rats

Carvalho S., Cortez E., Stumbo A.C., Thole A., Caetano C., Marques R., Pelajo-Machado M., Cristóvao Porto L., Carvalho L.
Cell Biology International, 2008

The aim of this study was to investigate laminin expression during liver regeneration induced by partial hepatectomy followed by bone marrow mononuclear cell (BMMNC) transplantation (injected into recently hepatectomyzed rats via the portal vein). Results showed that 15 min after partial hepatectomy, a transplanted CD34+ HSC was found in contact with laminin, which was localized in the portal and centrolobular veins of rat livers. Furthermore, 1 and 3 days after hepatectomy, transplanted BMMNCs were found in the hepatic sinusoids (endothelia) expressing laminin. These results strongly suggest that laminin might be an important extracellular matrix component for bone marrow cell attachment and migration in the injured liver.


Release of Matrix Metalloproteinase-8 During Physiological Trafficking and Induced Mobilization of Human Hematopoietic Stem Cells

Steinl C., Essl M., Schreiber T.D., Geiger K., Prokop L., Stevanovic´ S., Pötz O., Abele H., Wessels J.T, Aicher W.K., Klein G.
Stem Cells Dev., 2013

In the present study, we provide evidence that the collagenase MMP-8 is involved in stem cell mobilization. Cell–matrix adhesion assays were performed with LM-511 where MACS-isolated CD34+ cells were allowed to attach to immobilized LM-511. A rapid release of MMP-8 from isolated neutrophil granulocytes can be observed during an in vitro culture. Activated MMP-8 degrades LM-511 but without influencing the HSC progenitor–matrix adhesion. This since MMP-8 strongly digests the LM-a5 chain but leaves the LG1–3 domains intact.


Differential Expression of Basement Membrane Components in Lymphatic Tissues

Määttä M., Liakka A., Salo S., Tasanen K., Bruckner-Tuderman L., Autio-Harmainen H.
Journal of Histochemistry & Cytochemistry

Here the authors studied the distribution of various laminin-511 and different types of collagens in human spleen, lymph node, and tonsil to clarify their chain-specific distribution. The most widely distributed proteins in all these organs were laminin chains and collagen types IV and XVIII, which were present in practically all compartments. Conversely, LN a1, a2 and a4 and type VII collagen showed a more restricted expression pattern. A unique feature was that laminin-332, which normally are not localized to the vascular wall in non-lymphatic tissues, were present also in capillary basement membranes (BMs) of the follicular structures of lymph node. The results indicate that basement membranes of lymphatic tissues contain a variety of macromolecules that probably contribute strongly to immunological events. In addition, capillaries of the lymphoid tissue exhibit a specified BM composition resembling that in epithelial BMs of non-lymphoid tissues.