The Urokinase-receptor (CD87) Is Expressed in Cells of the Megakaryoblastic Lineage

Abstract

SummaryMegakaryocytopoiesis is governed in the bone marrow microenvironment by cellular interactions that include various adhesion receptor systems and pericellular proteolysis for proper regulation of cell motility and differentiation. In order to define the role of cell surface molecules required for these processes, we searched for protease receptors on these cells. In an in vitro system utilizing different cell lines of the megakaryoblastic lineage (MEG-01, Dami), low level surface expression of the urokinase (uPA) receptor was noted. Following stimulation with phorbolester (PMA), a 3-6 fold higher expression of uPA receptor over a period of up to 5 days could be observed by fluorescent activated cell-sorting as well as by direct ligand-binding of amino-terminal fragment of uPA or vitronectin. Together with elevated expression of αIIbβ3-integrin (glycoprotein IIb/IIIa complex), double immuno-fluorescence staining of stimulated cells confirmed the increased cell surface localization of uPA receptor. Semi-quantitative RT-PCR, ligand blot analysis and measurement of cell-bound proteolytic activity revealed a differentiation-dependent upregulation of the uPA receptor expression in megakaryoblastic cell lines as in monocytic cells. Due to its glycolipid anchorage, incubation with phosphatidyl-inositol-specific phospholipase C reduced uPA receptor-mediated ligand binding by about 60%. uPA receptor mRNA was expressed in cultured megakaryocytes derived from bone marrow, whereas no uPA receptor mRNA was detectable in platelets. These results indicate a differentiation-dependent increase in the expression of uPA receptor in megakaryoblastic cells. The characteristics of surface expression and functionality of the receptor on megakaryocytic cells may influence their maturation by regulating cellular communication in the bone marrow micro-environment.

Analysis of soluble urokinase plasminogen activator receptor in multiple myeloma for predicting prognosis

“…To date, it is unclear how suPAR is formed. As mononuclear cells and neutrophils exhibit uPAR expression, it was proposed that suPAR in healthy individuals may be derived from cell ageing, cell death, differentiation of the bone marrow, and the formation of megakaryocytes and platelets (23,24). Previous studies have also demonstrated that the elevated suPAR levels, observed in patients with cancer, are associated with a poor outcome (25).…”

Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in nonalcoholic fatty liver disease

“…11,12 uPAR is expressed by a wide range of immune cells whereas suPAR can be detected in different body fluids, including serum and plasma. [11][12][13][14][15][16][17] Cell-surface uPAR expression is up-regulated upon stimulation with growth factors and cytokines such as interleukin-1β and tumor necrosis factor. 18,19 The full length suPAR shed from the cell surface contains three domains (DI-III), and suPAR can occur in different cleaved forms consisting of only DI or DII-III, with partly divergent biological functions.…”

Soluble urokinase receptor released from human carcinoma cells: A plasma parameter for xenograft tumour studies

“…uPAR is known to be displayed on the surface of human blood monocytes and neutrophils (Plesner et al, 1997), so that senescence of these cells could be one source of suPAR in blood. The differentiation of megakaryocytes and formation of platelets in bone marrow may also contribute significant levels of suPAR to the blood compartment (Wohn et al, 1997).…”