| title: | CHARACTERIZATION OF LAMININ-8 AND -9 EXPRESSION AND FUNCTIONS IN HUMAN BLOOD AND NERVE CELLS |
|---|---|
| reg no: | ETF5211 |
| project type: | Estonian Science Foundation research grant |
| subject: |
1.6. Physical, Analytical and Inorganic Chemistry 3. Medical Sciences |
| status: | completed |
| institution: | University of Tartu |
| head of project: | Sulev Ingerpuu |
| duration: | 01.01.2002 - 31.12.2004 |
| description: | Laminins are the family of extracellular matrix proteins implicated in diverse functions of cells including adhesion, migration, proliferation, differentiation, and programmed cell death. Laminins are heterotrimeric molecules which consist of , and subunits. At present are known 14 laminin isoforms. The latest studies demonstrate that different laminins are synthezised in addition to epithelial cells also by endothelial, bone marrow stromal and blood cells. We were able to demonstrate for the first time that human platelets, lymphocytes and monocytes as well as several lymphoid and monocytic cell lines synthezise and can also secrete laminin-8 ( 4 1 1) following stimulation. We have shown that platelets and monocytes attach to laminin-8 via 6 1 integrin. Human lymphocytes are able to migrate on laminin-8 and this protein acts on T-cells as costimulator of proliferation. Laminin-8 enhances monocyte migration through artificial membrane. It is not known which is the laminin-8 function in mammalian tissues. The platelet laminin-8 may be used by them as adhesive and/or signalling molecule. It can participate in platelet attachment to endothelium or mediate their interaction during thrombus formation. The platelet laminin may have a role in inflammation process and cancer cell metastasis. The blood monocytes may use laminin-8 in many functions as extravasation into tissue, presentation of antigens, phagocytosis and production of inflammatory mediators. The laminin 4 chain is still very poorly characterized for the reason that there was no monoclonal antibodies (mAbs) available to this polypeptide until recently. We have developed first the mouse hybridoma cell lines which produce mAbs specific to 4 chain. These mAbs make possible also to study laminin-9 ( 4 2 1 ) which expression, localization and functions are even less known than for laminin-8. Our experiments have shown that human nerve stem cells adhere to human laminin-8 but it's relevance in nerve cell physiology is absolutely unclear. The aim of the present project is: *** to detect other laminin isoforms from platelets and mononuclear cells besides to laminin-8, *** to find out where the laminin synthesis takes place in blood cells and where it is stored, *** to study the mechanism of laminin secretion, *** to define which are the laminin-8 receptors and which are the receptor interaction domains on laminin-8, *** to study which is the role of 4 chain in laminin-8 functions and which are the most critical sites of the 4 molecule in physiological functions, *** to define which are the platelet, monocyte and lympocyte functions where laminin-8 is contributing, *** to find out does laminin-8 secreted by platelets participate in platelet interaction to neutrophils, *** to find out whether laminin-8 could be one of factors promoting angiogenesis, *** to study a role of laminin-8 in nerve cell attachment, projections outgrowth, proliferation and differentiation.. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Sulev Ingerpuu | University of Tartu, IMCB | researcher | |
| 2. | Erkki Juronen | IGMP | senior researcher | |
| 3. | Ain Kaare | University of Tartu, Children clinic | intensive haematology, physician | |
| 4. | Alar Sünter | IGMP | researcher | |