Regulation of leukocyte adherence and migration by glycosylphosphatidyl-inositol-anchored proteins

Sendo, Fujiro; Araki, Yoshihiko

doi:10.1002/jlb.66.3.369

Cited by 37 publications

(21 citation statements)

References 58 publications

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“…It has previously been shown that the GPI-80 is a possible regulatory molecule of cell adhesion and migration. [18][19][20] GPI-80 protein has a high sequence homology with Vanin-1, 21) which is expressed on perivascular thymic stromal cells and is involved in thymus homing in mice. 22) There is about 60% molecular homology between GPI-80 and Vanin-1, and these two molecules share a similar function in the sense that both may be involved in the regulation of leukocyte trafficking.…”

Section: Discussionmentioning

confidence: 99%

Glycosylphosphatidyl inositol‐anchored protein (GPI‐80) gene expression is correlated with human thymoma stage

et al. 2003

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Thymoma is one of the most common solid tumors in the mediastinum. Because there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular-genetic analysis of patients' tissues. Recent reports showed that genetic aberrations in thymoma were most frequently seen in chromosome 6q regions. We investigated the use of oligonucleotide arrays to monitor in vivo expression levels of genes in chromosome 6 regions in early- hymoma is a neoplasm of thymic epithelial cells mixed with lymphocytes. Although thymomas are usually encapsulated, some are characterized by locally invasive growth, pleural dissemination, or extrathoracic metastasis. However, there seems to be no cytological difference between noninvasive thymoma and invasive/metastatic thymoma.1-3) Several approaches have been made to differentiate non-invasive thymoma from invasive/metastatic thymoma, but the issue still remains controversial. Malignancy is generally evaluated in terms of the tumor's macroscopic invasiveness seen at the time of surgery.The elucidation of the genetic events underlying the initiation and progression of human thymoma has been hampered by limitations inherent in both in vitro and in vivo methods of study. The most significant limitation of in vitro-based systems is that there is no typical cell line for human thymoma. Also, genetic information derived from cell lines may not accurately reflect the molecular events taking place in the tissues from which they were derived. Examining tumors for alterations in gene expression is a potentially useful approach to identifying molecular differences between early-and late-stage thymomas. The advent of high-density oligonucleotide microarray technology, 4) with its capacity for simultaneous monitoring of thousands of genes, provides a unique opportunity for high-throughput genetic analysis of tumors. [5][6][7][8][9][10][11][12]

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Section: Discussionmentioning

confidence: 99%

Glycosylphosphatidyl inositol‐anchored protein (GPI‐80) gene expression is correlated with human thymoma stage

et al. 2003

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“…Structural characterization of uPAR has shown that it is a glycosylated single polypeptide linked to the plasma membrane by a GPI anchor (37). Several GPI-anchored proteins are known to regulate cellular activation, adhesion, and migration (38), even though GPI anchors only penetrate the outer leaflet of the plasma membrane and thus have no direct access to cytoplasmic signaling intermediates. The ability of uPAR to complex with membrane-spanning proteins has suggested that uPAR can initiate leukocyte activation by appropriating the signaling mechanisms of a partner protein such as CR3, in effect using it as a signal transduction device.…”

Section: Discussionmentioning

confidence: 99%

Clustering of Urokinase Receptors (uPAR; CD87) Induces Proinflammatory Signaling in Human Polymorphonuclear Neutrophils

Sitrin

Pan

Harper

et al. 2000

The Journal of Immunology

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Leukocytes use urokinase receptors (uPAR; CD87) in adhesion, migration, and proteolysis of matrix proteins. Typically, uPAR clusters at cell-substratum interfaces, at focal adhesions, and at the leading edges of migrating cells. This study was undertaken to determine whether uPAR clustering mediates activation signaling in human polymorphonuclear neutrophils. Cells were labeled with fluo-3/AM to quantitate intracellular Ca2+ ([Ca2+]i) by spectrofluorometry, and uPAR was aggregated by Ab cross-linking. Aggregating uPAR induced a highly reproducible increase in [Ca2+]i (baseline to peak) of 295 ± 37 nM (p = 0.0002). Acutely treating cells with high m.w. urokinase (HMW-uPA; 4000 IU/ml) produced a response of similar magnitude but far shorter duration. Selectively aggregating uPA-occupied uPAR produced smaller increases in [Ca2+]i, but saturating uPAR with HMW-uPA increased the response to approximate that of uPAR cross-linking. Cross-linking uPAR induced rapid and significant increases in membrane expression of CD11b and increased degranulation (release of β-glucuronidase and lactoferrin) to a significantly greater degree than cross-linking control Abs. The magnitude of degranulation correlated closely with the difference between baseline and peak [Ca2+]i, but was not dependent on the state of uPA occupancy. By contrast, selectively cross-linking uPA-occupied uPAR was capable of directly inducing superoxide release as well as enhancing FMLP-stimulated superoxide release. These results could not be duplicated by preferentially cross-linking unoccupied uPAR. We conclude that uPAR aggregation initiates activation signaling in polymorphonuclear neutrophils through at least two distinct uPA-dependent and uPA-independent pathways, increasing their proinflammatory potency (degranulation and oxidant release) and altering expression of CD11b/CD18 to favor a firmly adherent phenotype.

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“…[50][51][52][53][54] Integrins mediate cell adhesion, migration, phagocytosis, and virtually all PMN functions. To accomplish their roles, integrins must act not only as individual receptors, but also as components of supramolecular complexes at the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

CD157 is an important mediator of neutrophil adhesion and migration

Funaro¹,

Ortolan²,

Ferranti³

et al. 2004

Blood

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CD157, a glycosylphosphatidylinositol (GPI)-anchored protein encoded by a member of the CD38 NADase/ADP-ribosyl cyclase gene family, is expressed on the surface of most human circulating neutrophils. This work demonstrates that CD157 is a receptor that induces reorganization of the cytoskeleton and significant changes in cell shape, and that signals mediated by CD157 act through modulation of cytosolic Ca 2؉ concentration. These signals are independent of the products of CD157's enzymatic activities (ie, cyclic adenosine diphosphate [ADP]-ribose and ADP-ribose). Indeed, the enzymatic activities of CD157 in circulating neutrophils as well as in dimethyl sulfoxide (DMSO)-differentiated (CD157 ؉ / CD38 ؊ ) HL-60 cells, are hardly detectable. This work also shows that the receptorial activity relies on cross-talk between CD157 and ␤ 2 integrin. CD157 localizes in GM1-enriched lipid rafts and, upon activation, it migrates to the uropod, a structure specialized in motility and adhesive functions. Indeed, CD157 is involved in adhesion to extracellular matrix proteins and in chemotaxis induced in vitro by formylmethionyl-leucyl-phenylalanine (fMLP). These findings were consistent with the results obtained in neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH), in which CD157 is deficient. These neutrophils showed constant defects in adhesion and migration. Our data attribute specific and crucial roles to CD157 in the regulation of innate immunity during inflammation. IntroductionHuman CD157 is a glycosylphosphatidylinositol (GPI)-linked glycoprotein encoded by a member of the NADase/adenosine diphosphate (ADP)-ribosyl cyclase gene family, which also includes CD38. 1 The CD157 and CD38 molecules are pleiotropic in function, acting both as ectoenzymes and receptors. [2][3][4] CD157 is abundantly expressed by myeloid lineage from precursors to differentiated stages 5 by bone marrow stromal cells, synovial cells, endothelial cells, and other cell types. 6 Functional analysis by means of agonistic monoclonal antibodies (mAbs) mimicking natural ligand(s) suggested that CD157 could act as a receptor with signal transduction capacity. However, as CD157 lacks a cytoplasmic domain, it must associate with some "conventional" receptor(s) to transduce signals; much in the same way as CD38, which has a short intracellular domain, CD157 acts as a parasite on specific receptors to compensate for its structural ineptitude to exert receptorial functions. 7,8 In concert with monocytes and tissue macrophages, neutrophils carry out many of the major functional responses of the innate immune system. They participate in inflammatory responses, such as host resistance to infection, and in detrimental host inflammatory reactions, including arthritis, septic shock, stroke, and transplantation rejection. The regulation of neutrophil recruitment into the inflammatory sites and neutrophil clearance are critical processes assuring effective host defense without tissue injury. Neutrophil extravasation is a multistep process depe...

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Regulation of leukocyte adherence and migration by glycosylphosphatidyl-inositol-anchored proteins

Cited by 37 publications

References 58 publications

Glycosylphosphatidyl inositol‐anchored protein (GPI‐80) gene expression is correlated with human thymoma stage

Glycosylphosphatidyl inositol‐anchored protein (GPI‐80) gene expression is correlated with human thymoma stage

Clustering of Urokinase Receptors (uPAR; CD87) Induces Proinflammatory Signaling in Human Polymorphonuclear Neutrophils

CD157 is an important mediator of neutrophil adhesion and migration

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