Urokinase receptors in human monocytes

Nykjær, Anders; Petersen, Claus Munck; Christensen, Erik; Davidsen, Ole; Gliemann, Jørgen

doi:10.1016/0167-4889(90)90149-8

Cited by 58 publications

(25 citation statements)

References 21 publications

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“…In contrast, tc-u-PA⅐PAI-1 complexes bind to LRP/␣ 2 MR with 10 -20-fold greater affinity than pro-UK (12,18) and are internalized preferentially; hence, the clearance of these complexes is selectively impaired in the presence of RAP. Indeed, the fact that relatively minor amounts of tc-u-PA⅐PAI-1 complexes were detectable on the surface of cells incubated with 125 I-pro-UK in the absence of RAP confirms reports demonstrating that these complexes are internalized rapidly (23,24,37,61,67). Furthermore, because tc-u-PA⅐PAI-1 complexes bind to uPAR with an affinity similar to that of pro-UK or tc-u-PA (60), the ongoing generation of complexes, in conjunction with selective inhibition of their clearance, results in an increased concentration of proteolytically inactive complexes that compete for binding to a fixed number of uPARs.…”

Section: Discussionsupporting

confidence: 67%

The Low Density Lipoprotein Receptor-related Protein/α2-Macroglobulin Receptor Regulates Cell Surface Plasminogen Activator Activity on Human Trophoblast Cells

Zhang¹,

Sakthivel²,

Kniss³

et al. 1998

Journal of Biological Chemistry

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The low density lipoprotein receptor-related protein/ ␣ 2 -macroglobulin receptor (LRP/␣ 2 MR) mediates the internalization of numerous ligands, including prourokinase (pro-UK) and complexes between two-chain urokinase (tc-u-PA) and plasminogen activator inhibitor type-1 (PAI-1). It has been suggested that through its ability to internalize these ligands, LRP/␣ 2 MR may regulate the expression of plasminogen activator activity on cell surfaces; this hypothesis, however, has not been experimentally confirmed. To address this issue, we assessed the ability of LRP/␣ 2 MR to regulate plasminogen activator activity on human trophoblast cells, which express both LRP/␣ 2 MR and the urokinase receptor (uPAR). Trophoblasts internalized and degraded exogenous 125 I-pro-UK (primarily following its conversion to tc-u-PA and incorporation into tc-u-PA⅐PAI complexes) in an LRP/␣ 2 MR-dependent manner, which was inhibited by the LRP/␣ 2 MR receptor-associated protein. Receptor-associated protein also caused a ϳ50% reduction in cell surface plasminogen activator activity and delayed the regeneration of unoccupied uPAR by cells on which uPAR were initially saturated with pro-UK. Identical effects were caused by anti-LRP/␣ 2 MR antibodies. These results demonstrate that LRP/␣ 2 MR promotes the expression of cell surface plasminogen activator activity on trophoblasts by facilitating the clearance of tc-u-PA⅐PAI complexes and regeneration of unoccupied cell surface uPAR.

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Section: Discussionsupporting

confidence: 67%

The Low Density Lipoprotein Receptor-related Protein/α2-Macroglobulin Receptor Regulates Cell Surface Plasminogen Activator Activity on Human Trophoblast Cells

Zhang¹,

Sakthivel²,

Kniss³

et al. 1998

Journal of Biological Chemistry

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“…Incubation of monocytes on uncoated plastic resulted in low-level accumulation of UPAR protein that was much less than in cells adherent to P-selectin (Fig. 1), suggesting that the use of plastic adhesion in isolation protocols may account for previous reports that UPAR is constitutively present on monocytes (27,28).…”

Section: Rapid Synthesis Of Upar Protein Is Induced By Adhesion Of Momentioning

confidence: 80%

Cell adhesion regulates gene expression at translational checkpoints in human myeloid leukocytes

Mahoney

Weyrich

Dixon

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Engagement of adhesion molecules on monocytes and other myeloid leukocytes, which are effector cells of the innate immune system, not only tethers the leukocytes in place but also transmits outside-in signals that induce functional changes and alter gene expression. We found that a subset of mRNAs that are induced or amplified by adhesion of human monocytes to P-selectin via its surface ligand, P-selectin glycoprotein 1, have characteristics that suggest specialized translational control. One of these codes for urokinase plasminogen activator receptor (UPAR), a critical surface protease receptor and regulator of cell adhesion and migration. Although UPAR transcripts are induced by adhesion, rapid synthesis of the protein uses constitutive mRNA without a requirement for new transcription and is regulated by mammalian target of rapamycin, demonstrating new biologic roles for the signaldependent translation pathway controlled by this intracellular kinase. The synthesis of UPAR in monocytic cells is also regulated by eukaryotic translation initiation factor 4E, a second key translational checkpoint, and phosphorylation of eukaryotic translation initiation factor 4E is induced by adhesion of monocytes to Pselectin. Translationally controlled display of UPAR by monocytes confers recognition of the matrix protein, vitronectin. Adhesiondependent signaling from the plasma membrane to translational checkpoints represents a previously unrecognized mechanism for regulating surface phenotype that may be particularly important for myeloid leukocytes and other cells that are specialized for rapid inflammatory and vascular responses.

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“…Leukocytes express uPA (5)(6)(7)(8) and also specific receptors for uPA on the cell surface (9,10). uPA converts the inactive proenzyme plasminogen to plasmin, a protease of broad substrate specificity (11).…”

mentioning

confidence: 99%

Cutting Edge: Antigen-Driven Lymphocyte Recruitment to the Lung Is Diminished in the Absence of Urokinase-Type Plasminogen Activator (uPA) Receptor, but Is Independent of uPA

Gyetko

Sud

Sonstein

et al. 2001

The Journal of Immunology

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The requirement for urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in T lymphocyte migration is unknown. uPA−/− mice have fewer pulmonary lymphocytes in response to certain infections, but its unknown whether this is due to diminished recruitment. Primed, recipient mice were IT inoculated with Ag. Three days later, fluorescently labeled lymphoblasts from background-matched control wild-type (WT), uPA−/−, or uPAR−/− donor mice were injected i.v., and their recruitment was determined. Approximately twice the number of uPA−/− compared with WT lymphoblasts were recruited to the lungs of WT recipients. This difference was eliminated when uPA−/− and WT lymphoblasts were injected into uPA−/− recipients. Thus, the reduced number of lung lymphocytes in infected uPA−/− mice is not due to reduced recruitment. However, uPAR is critically involved in recruitment. Markedly fewer uPAR−/− compared with WT lymphoblasts were recruited to the lung. These findings suggest that uPAR may be a novel target for immune modulation in T lymphocyte-mediated disorders.

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Urokinase receptors in human monocytes

Cited by 58 publications

References 21 publications

The Low Density Lipoprotein Receptor-related Protein/α2-Macroglobulin Receptor Regulates Cell Surface Plasminogen Activator Activity on Human Trophoblast Cells

The Low Density Lipoprotein Receptor-related Protein/α2-Macroglobulin Receptor Regulates Cell Surface Plasminogen Activator Activity on Human Trophoblast Cells

Cell adhesion regulates gene expression at translational checkpoints in human myeloid leukocytes

Cutting Edge: Antigen-Driven Lymphocyte Recruitment to the Lung Is Diminished in the Absence of Urokinase-Type Plasminogen Activator (uPA) Receptor, but Is Independent of uPA

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