Adenosine Triphosphate–Induced Shedding of CD23 and L-Selectin (CD62L) From Lymphocytes Is Mediated by the Same Receptor but Different Metalloproteases

Gu, Ben; Bendall, Linda J.; Wiley, James S.

doi:10.1182/blood.v92.3.946

Cited by 162 publications

(65 citation statements)

References 35 publications

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“…To our surprise, therefore, in conducting equivalent experiments using lymphocytes from GSK P2X 7 Ϫ/Ϫ mice, we have found that T cells in this strain exhibit high levels of P2X 7 activity. Moreover, unlike previous studies, the activity we report here is unambiguously that of the genuine P2X 7 receptor, reflecting the unique ability of this channel to evoke, when stimulated, the rapid translocation of phosphatidylserine (PS) to the cell surface and cell death [2,15], as well as shedding of the lymphocyte homing receptor CD62 ligand (CD62L) [16].…”

Section: Introductioncontrasting

confidence: 67%

Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses

Taylor

González-Begné

Sojka

et al. 2009

Journal of Leukocyte Biology

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The purinergic receptor P2X 7 is expressed on immune cells, and its stimulation results in the release of IL-1␤ from macrophages. Its absence, as evidenced from the analysis of two independent strains of P2X 7 -deficient mice, results in reduced susceptibility to inflammatory disease, and the molecule is an important, potential therapeutic target in autoimmunity. However, P2X 7 has also been detected in several neuronal cell types, although its function and even its presence in these cells are highly contested, with anti-P2X 7 antibodies staining brain tissue from both strains of P2X 7 ؊/؊ mice identically to wild-type mice. It has therefore been suggested that neurons express a distinct "P2X 7 -like" protein that has similar antibody recognition epitopes to P2X 7 and some properties of the genuine receptor. In this study, we show that whereas P2X 7 activity is absent from macrophages and dendritic cells in P2X 7 ؊/؊ animals, T cells from one gene-deficient strain unexpectedly exhibit higher levels of P2X 7 activity than that found in cells from control, unmanipulated C57BL/6 mice. A potential mechanism for this tissue-specific P2X 7 expression in P2X 7 ؊/؊ animals is discussed, as is the implication that the immune and indeed neuronal functions of P2X 7 may have been underestimated. J. Leukoc. Biol. 85: 978 -986; 2009.

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Section: Introductioncontrasting

confidence: 67%

Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses

Taylor

González-Begné

Sojka

et al. 2009

Journal of Leukocyte Biology

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“…A possible candidate is a 'chemoattractant/chemokine' synthesized or released by endothelial cells. Extracellular ATP can stimulate the shedding of L-selectin as well as CD23 from lymphocytes (Gu et al, 1998) and since ATP can be secreted from endothelial cells (Milner et al, 1990), the role of purinergic mechanisms in transendothelial migration was studied. Thus lymphocytes were pretreated with oxATP to irreversibly inactivate the P2Z/P2X 7 receptor (Murgia et al, 1993;Wiley et al, 1994) prior to the migration assay.…”

Section: Discussionmentioning

confidence: 99%

Transendothelial migration of lymphocytes in chronic lymphocytic leukaemia is impaired and involved down‐regulation of both L‐selectin and CD23

Chen

Dao

et al. 1999

Br J Haematol

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Summary.Chronic lymphocytic leukaemia (B-CLL) is characterized by a progressive accumulation of B lymphocytes in blood and bone marrow and high concentrations of soluble CD23 and L-selectin are found in the serum of these patients. In this study lymphocytes from normal subjects and patients with B-CLL were allowed to undergo transendothelial migration across confluent layers of human umbilical vein endothelial cells. Lymphocytes in B-CLL samples showed an impaired capacity to migrate while the minor proportion of normal T cells was enriched by a mean of 2·5-fold in the transmigrated lymphocytes. In contrast, the ratio of B to T lymphocytes in normal preparations was unchanged in the transmigrated population. The expression of adhesion molecules on B-CLL lymphocytes before and after transendothelial migration was studied by flow cytometry which showed that 71 Ϯ 5% of L-selectin was lost from the surface of transmigrated lymphocytes. T and B cells from normal subjects also showed a major loss of L-selectin after transmigration. B-CLL lymphocytes and normal B cells expressed CD23 but this molecule was down-regulated following transendothelial migration, whereas the expression of VLA-4, ICAM-1, LFA-1 and CD44 was unchanged. Lymphocytes incubated with oxidized ATP, an irreversible inhibitor of P2Z/P2X7 purinoceptors, retained their capacity for transendothelial migration and showed the same loss of L-selectin as control leukaemic lymphocytes. Our results show that B-CLL lymphocytes have impaired ability for transendothelial migration compared to normal peripheral blood lymphocytes. Moreover, transendothelial migration involves a universal loss of L-selectin and CD23 from lymphocytes which suggests that the high serum levels of soluble L-selectin and CD23 observed in B-CLL may be generated by shedding during the process of transendothelial migration.

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“…Some CD23 material with apparent high molecular weight was also detected in cell-free supernatants. This diffuse smear could come from multimeric forms of shorter sCD23 fragments often observed after SDS-PAGE separation (46). Cathepsin G treatment also led to the release of essentially short fragments (not shown).…”

Section: Fragments Released By Hlementioning

confidence: 92%

Proteases produced by activated neutrophils release soluble CD23 fragments endowed with proinflammatory effects

et al. 2001

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Polymorphonuclear neutrophils (PMNs) are the major source of proteolytic activities involved mainly in tissue injuries observed in chronic inflammatory disorders. High levels of soluble forms of CD23 (the low-affinity receptor for IgE) were found in biological fluids from these patients, and recent reports focused on a CD23-mediated regulation of inflammatory response. In this context, we show here that co-culture of activated PMN with CD23+ B cells resulted in a drastic release of soluble CD23 fragments from the cell surface. This cleavage was inhibited by serine proteases inhibitors, including a1-antitrypsin. We next demonstrated that purified human leukocyte elastase or cathepsin G efficiently cleaved membrane CD23 on B cells with a high specificity. Soluble fragments released by serine proteases-mediated CD23 proteolysis stimulated resting monocytes to produce oxidative burst and proinflammatory cytokine without any co-stimulatory signal. This work strongly supports the idea that the capacity of PMN-derived proteases to release soluble forms of CD23 participates in the inflammatory process mediated by these cells.

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Adenosine Triphosphate–Induced Shedding of CD23 and L-Selectin (CD62L) From Lymphocytes Is Mediated by the Same Receptor but Different Metalloproteases

Cited by 162 publications

References 35 publications

Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses

Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses

Transendothelial migration of lymphocytes in chronic lymphocytic leukaemia is impaired and involved down‐regulation of both L‐selectin and CD23

Proteases produced by activated neutrophils release soluble CD23 fragments endowed with proinflammatory effects

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