Leukocyte Homing to Synovium

2000 ◽  
pp. 133-167 ◽  
Author(s):  
D.D. Patel ◽  
B.F. Haynes
Keyword(s):  
Leukocyte Homing

scholarly journals Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons.

1995 ◽  
Vol 131 (6) ◽  
pp. 1623-1633 ◽  
Author(s):  
K L Bennett ◽  
B Modrell ◽  
B Greenfield ◽  
A Bartolazzi ◽  
I Stamenkovic ◽  
...  
Keyword(s):  
Regulatory Mechanism ◽  
Protein Glycosylation ◽  
Differential Splicing ◽  
Binding Studies ◽  
Lectin Activity ◽  
Cd44 Isoforms ◽  
Binding Function ◽  
Glycosylation Inhibitor ◽  
Immunoglobulin Domain ◽  
Leukocyte Homing

The hyaluronan (HA)-binding function (lectin function) of the leukocyte homing receptor, CD44, is tightly regulated. Herein we address possible mechanisms that regulate CD44 isoform-specific HA binding. Binding studies with melanoma transfectants expressing CD44H, CD44E, or with soluble immunoglobulin fusions of CD44H and CD44E (CD44H-Rg, CD44E-Rg) showed that although both CD44 isoforms can bind HA, CD44H binds HA more efficiently than CD44E. Using CD44-Rg fusion proteins we show that the variably spliced exons in CD44E, V8-V10, specifically reduce the lectin function of CD44, while replacement of V8-V10 by an ICAM-1 immunoglobulin domain restores binding to a level comparable to that of CD44H. Conversely, CD44 bound HA very weakly when exons V8-V10 were replaced with a CD34 mucin domain, which is heavily modified by O-linked glycans. Production of CD44E-Rg or incubation of CD44E-expressing transfectants in the presence of an O-linked glycosylation inhibitor restored HA binding to CD44H-Rg and to cell surface CD44H levels, respectively. We conclude that differential splicing provides a regulatory mechanism for CD44 lectin function and that this effect is due in part to O-linked carbohydrate moieties which are added to the Ser/Thr rich regions encoded by the variably spliced CD44 exons. Alternative splicing resulting in changes in protein glycosylation provide a novel mechanism for the regulation of lectin activity.

scholarly journals HIV-1 Nef and Vpu Interfere with L-Selectin (CD62L) Cell Surface Expression To Inhibit Adhesion and Signaling in Infected CD4+T Lymphocytes

2015 ◽  
Vol 89 (10) ◽  
pp. 5687-5700 ◽  
Author(s):  
Lia Vassena ◽  
Erica Giuliani ◽  
Herwig Koppensteiner ◽  
Sebastian Bolduan ◽  
Michael Schindler ◽  
...  
Keyword(s):  
T Cells ◽  
Plasma Membrane ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Viral Proteins ◽  
Peripheral Lymph ◽  
Leukocyte Homing ◽  
Hiv 1

ABSTRACTLeukocyte recirculation between blood and lymphoid tissues is required for the generation and maintenance of immune responses against pathogens and is crucially controlled by the L-selectin (CD62L) leukocyte homing receptor. CD62L has adhesion and signaling functions and initiates the capture and rolling on the vascular endothelium of cells entering peripheral lymph nodes. This study reveals that CD62L is strongly downregulated on primary CD4+T lymphocytes upon infection with human immunodeficiency virus type 1 (HIV-1). Reduced cell surface CD62L expression was attributable to the Nef and Vpu viral proteins and not due to increased shedding via matrix metalloproteases. Both Nef and Vpu associated with and sequestered CD62L in perinuclear compartments, thereby impeding CD62L transport to the plasma membrane. In addition, Nef decreased total CD62L protein levels. Importantly, infection with wild-type, but not Nef- and Vpu-deficient, HIV-1 inhibited the capacity of primary CD4+T lymphocytes to adhere to immobilized fibronectin in response to CD62L ligation. Moreover, HIV-1 infection impaired the signaling pathways and costimulatory signals triggered in primary CD4+T cells by CD62L ligation. We propose that HIV-1 dysregulates CD62L expression to interfere with the trafficking and activation of infected T cells. Altogether, this novel HIV-1 function could contribute to virus dissemination and evasion of host immune responses.IMPORTANCEL-selectin (CD62L) is an adhesion molecule that mediates the first steps of leukocyte homing to peripheral lymph nodes, thus crucially controlling the initiation and maintenance of immune responses to pathogens. Here, we report that CD62L is downmodulated on the surfaces of HIV-1-infected T cells through the activities of two viral proteins, Nef and Vpu, that prevent newly synthesized CD62L molecules from reaching the plasma membrane. We provide evidence that CD62L downregulation on HIV-1-infected primary T cells results in impaired adhesion and signaling functions upon CD62L triggering. Removal of cell surface CD62L may predictably keep HIV-1-infected cells away from lymph nodes, the privileged sites of both viral replication and immune response activation, with important consequences, such as systemic viral spread and evasion of host immune surveillance. Altogether, we propose that Nef- and Vpu-mediated subversion of CD62L function could represent a novel determinant of HIV-1 pathogenesis.

Function and regulation of leukocyte homing receptors

1994 ◽  
Vol 55 (1) ◽  
pp. 133-140 ◽  
Author(s):  
Mark A. Jutila
Keyword(s):  
Leukocyte Homing

scholarly journals Non-invasive Imaging of Leukocyte Homing and Migration in vivo

10.3791/2062 ◽  
2010 ◽  
Author(s):  
Baomei Wang ◽  
Bernd H. Zinselmeyer ◽  
Jeremiah R. McDole ◽  
Peggy A. Gieselman ◽  
Mark J. Miller
Keyword(s):  
Non Invasive ◽  
And Migration ◽  
Leukocyte Homing

Leukocyte homing in DSS-induced colitis is reduced by MadCAM-1 blockade in vivo

2000 ◽  
Vol 118 (4) ◽  
pp. A573
Author(s):  
Stefan A. Farkas ◽  
Hans Herfarth ◽  
Matthias Roessle ◽  
Karl-Walter Jauch ◽  
Matthias Anthuber
Keyword(s):  
Leukocyte Homing

scholarly journals Homeodomain Factor Nkx2-3 Controls Regional Expression of Leukocyte Homing Coreceptor MAdCAM-1 in Specialized Endothelial Cells of the Viscera

2000 ◽  
Vol 224 (2) ◽  
pp. 152-167 ◽  
Author(s):  
Cheng-Chun Wang ◽  
Christine Biben ◽  
Lorraine Robb ◽  
Fatiha Nassir ◽  
Louise Barnett ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Leukocyte Homing

scholarly journals Structure of the Regulatory Hyaluronan Binding Domain in the Inflammatory Leukocyte Homing Receptor CD44

2004 ◽  
Vol 13 (4) ◽  
pp. 483-496 ◽  
Author(s):  
Peter Teriete ◽  
Suneale Banerji ◽  
Martin Noble ◽  
Charles D. Blundell ◽  
Alan J. Wright ◽  
...  
Keyword(s):  
Binding Domain ◽  
Homing Receptor ◽  
Leukocyte Homing ◽  
Hyaluronan Binding
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