Activation of Human Leukocytes Reduces Surface P-Selectin Glycoprotein Ligand-1 (PSGL-1, CD162) and Adhesion to P-Selectin In Vitro

Davenpeck, Kelly L.; Brummet, Mary; Hudson, Sherry A.; Mayer, Ruth; Bochner, Bruce S.

doi:10.4049/jimmunol.165.5.2764

Cited by 114 publications

(115 citation statements)

References 40 publications

(44 reference statements)

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“…It has been suggested that the way SELPLG is distributed on the leukocyte surface, and not the amount, is important for adhesion of leukocytes to P-selectin (Bruehl et al 1997;Lorant et al 1995). Moreover, SELPLG in the circulation could derive either from the release of SELPLG from leukocyte surfaces or from its release after the initiation of leukocyte rolling (Davenpeck et al 2000). In the first case, higher circulating levels would reflect decreased leukocyte binding capacity to P-selectin, and would be associated with a lower risk of CAD.…”

Section: Discussionmentioning

confidence: 99%

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SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease

Trégouët

Barbaux

Poirier

et al. 2003

Annals of Human Genetics

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SummaryP-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand) constitute a receptor/ligand complex that is likely to be involved in the development of atherosclerosis and its complications. While the genetic variability of P-selectin has already been investigated in depth, that of the SELPLG gene has not yet been extensively explored. The coding and regulatory sequences of the SELPLG were screened and nine polymorphisms were identified. The identified polymorphisms were genotyped in the AtheroGene study, a case-control study of coronary artery disease (CAD). Haplotype analysis revealed that two polymorphisms of SELPLG, the M62I and the VNTR, independently influenced plasma SELPLG levels. Conversely, haplotypes of SELPLG were not associated with CAD risk.

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Section: Discussionmentioning

confidence: 99%

“…SELPLG is a dimeric mucinlike glycoprotein expressed on all leukocyte surfaces, constituted by two monomers of molecular mass of ∼ 120-kDa (Moore et al 1992). A human soluble SELPLG has been described which is released after leukocyte activation (Davenpeck et al 2000).…”

Section: Introductionmentioning

confidence: 99%

SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease

Trégouët

Barbaux

Poirier

et al. 2003

Annals of Human Genetics

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“…The reports that PSGL-1 can be processed by a protease [15,16] and that PSGL-1 could be a candidate substrate for ADAM8 [17], in addition to our finding of PSGL-1/ADAM8 association, prompted us to investigate the potential involvement of ADAM8 in the cleavage of PSGL-1. Experiments with neutrophils incubated with activated sADAM8 showed a significant diminution in the membrane expression of PSGL-1 ( Fig.…”

Section: Proteolytic Cleavage Of Psgl-1 By Adam8mentioning

confidence: 99%

The metalloprotease ADAM8 is associated with and regulates the function of the adhesion receptor PSGL‐1 through ERM proteins

et al. 2011

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The P-selectin glycoprotein ligand-1 (PSGL-1) is involved in the initial contact of leukocytes with activated endothelium, and its adhesive function is regulated through its proteolytic processing. We have found that the metalloprotease ADAM8 is both associated with PSGL-1 through the ezrin-radixin-moesin actin-binding proteins and able to cause the proteolytic cleavage of this adhesion receptor. Accordingly, ADAM8 knockdown increases PSGL-1 expression, and functional assays show that ADAM8 is able to reduce leukocyte rolling on P-selectin and hence on activated endothelial cells. We conclude that ADAM8 modulates the expression and function of PSGL-1.Key words: ADAM8 . Adhesion . Cell migration . ERM . Neutrophil . PSGL-1 See accompanying Commentary by Zarbock and RossaintIntroduction ADAM family is a group of transmembrane glycoproteins that possess proteolytic and signaling properties and are implicated in both cell adhesion and cell fusion processes [1]. ADAMs are usually activated by furin or other convertases as well as autocatalytically, in the case of ADAM8 [2]. It has been described that ADAM8 cleaves important cell surface proteins [3,4], cytokines and growth factors [5]. ADAM8 is overexpressed under several pathological conditions involving inflammation and remodeling of the extracellular matrix, including malignant diseases and asthma [6][7][8].P-selectin glycoprotein ligand-1 (PSGL-1), through its interaction with P-, E-and L-selectins, mediates the tethering and rolling of leukocytes on endothelial cells prior to their extravasation [9,10], triggers the activation of transcription factors like cFos [11] in leukocytes and induces the generation of tolerogenic DCs which promote the differentiation of Treg cells [12]. Although it was described that PSGL-1 was a substrate of the proteases BACE1 and ADAM10 [13], neither the physiological context of cleavage nor the mechanism responsible for its shedding have been identified so far. In this work, we demonstrate that in leukocytes SHORT COMMUNICATION Ã These authors contributed equally to this work. 3436Frontline ADAM8 associates with PSGL-1 through ezrin-radixin-moesin (ERM) proteins, and that this interaction modulates the expression and function of this adhesion receptor. Results and discussionAssociation of PSGL-1 with ADAM8To identify intracellular molecules able to associate with PSGL-1, we performed a proteomic analysis of HL-60 cell lysates pulled down with the cytoplasmic tail of PSGL-1 fused to GST (GST-PSGL-1cyt) [11]. This analysis revealed the presence of a 98-kDa protein that corresponded to ADAM8 (data not shown). Additional pull-down experiments performed with fragments of the cytoplasmic tail of PSGL-1 fused to GST, detected an additional protein of 75-80 kDa, which likely corresponded to a cleaved form of ADAM8 (Fig. 1A, left panel). To map the region of PSGL-1 involved in this interaction, pull-down experiments from lysates of HL-60 cells were performed with different fragments of the cytoplasmic tail of PSGL-1 fused to GST. We found th...

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“…These processes are critical for eosinophil interaction to activated vascular endothelium as well as for migration and tissue localization and are also implicated in a range of effectors functions by these cells (Schleimer et al 1992 (Davenpeck et al 2000). The hypothesis that the primary function of eosinophils is to defend hosts against infection by relatively large organisms such as parasitic helminths is based on the accumulation of observations that: (1) eosinophils degranulation can kill helminths in vitro in the presence of antibody and/or complement; (2) they move from the blood and aggregate in the locality of helminths in vivo; (3) large numbers of eosinophils are often seen in close association with both intact and damaged helminths in vivo; and (4) they clearly degranulate in the vicinity of, or on to the surfaces of, helminths in vivo (Butterworth 1984).…”

Section: Herein We Have Focused Attention On Major Phenotypic Featurementioning

confidence: 99%

“…Besides L-selectin (CD62-L), the major molecule expressed on the surface of circulating leukocyte (Bevilacqua & Nelson 1993, Tedder et al 1995, eosinophils express a large number of adhesion molecules including integrins (LFA-1/CD18) and members of the immunoglobulin superfamily, such as ICAM-1 (CD54) (Bochner & Schleimer 1994). The counterligants for the selectins share common features of carbohydrate ligands for selectins, named Lewis X -related structures (Davenpeck et al 2000).…”

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confidence: 99%

High expression of co-stimulatory and adhesion molecules are observed on eosinophils during human Schistosoma mansoni infection

Silveira-Lemos

Teixeira-Carvalho

Martins‐Filho

et al. 2006

Mem. Inst. Oswaldo Cruz

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Herein we have focused attention on major phenotypic features of peripheral blood eosinophils from chronic Schistosoma mansoni-infected patients. For this purpose, detailed immunophenotypic profiles of a range of cell surface markers were performed, including activation markers (CD23/CD69/CD25/HLA-DR), co-stimulatory molecules (CD28/CD80/CD86), chemokine receptors (CXCR1/CXCR2/CCR3/CCR5) besides L-selectin-CD62L and adhesion molecules (CD18/CD54). Our major findings pointed out increased frequency of CD23 + -cells, besides decreased percentages of CD69 + -eosinophils, suggesting a chronic activation status with low frequency of early activated eosinophils in chronic S. mansoni-infected patients (INT) in comparison to non-infected individuals (NI). Moreover, a dichotomic expression of beta-chemokine receptors was observed during human schistosomiasis mansoni with higher CCR5 and lower levels of CCR3 observed between groups. Enhanced expression of co-stimulatory receptors (CD28/CD86) and adhesion molecules (CD54/CD18), besides striking lower frequency of L-selectin + were reported for eosinophils from INT group as compared to NI. Interestingly, the frequency of CD62L + -eosinophils and a range of cell activation related molecules pointed out an opposite pattern of association in NI and INT, where only INT patients that display lower frequency of CD62L + -eosinophils (first CD62L tertile) kept the unusual relationship between the expression of L-selectin and the CD23 activation marker. These findings suggest that distinct dynamic of activation markers expressed by eosinophils may occur during chronic S. mansoni infection.Key words: schistosomiasis -eosinophils -activation markers -L-selectin Eosinophils have been shown to play a major role in the immune response to helminthic infections (Butterworth et al. 1979, Hamann et al. 1987. In this context, transendothelial migration is essential for eosinophil recruitment from blood vessels into inflammatory tissues. At the inflammatory site, further interaction with invading parasites occurs via adherence with subsequent larval damage mediated by release of eosinophil toxic granular effector molecules, proinflammatory lipids, and cytokines (Greene et al. 1981, Medina-De la Garza et al. 1990, Strote et al. 1990, Brattig et al. 1991, Wildenburg et al. 1994. The prerequisite for adherence of effector eosinophils to parasite's larval stages is their sequential activation and chemotactic attraction that favor the eosinophils tethering. The migration of mature activated eosinophils from circulatory pools into the inflammatory foci depends on specific upregulation of adhesion molecules and chemokine receptors, which direct transmigration through a positive chemotactic gradient. This phenomenon seems to represent the key element for eosinophils recruitment that lead to accumulation of these proinflammatory cells that surround the parasite in its microenvironment (Pearlman 1997, Tachimoto et al. 2000.The profile of cell surface molecules expression on mature eosinophils resembles...

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Activation of Human Leukocytes Reduces Surface P-Selectin Glycoprotein Ligand-1 (PSGL-1, CD162) and Adhesion to P-Selectin In Vitro

Cited by 114 publications

References 40 publications

SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease

SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease

The metalloprotease ADAM8 is associated with and regulates the function of the adhesion receptor PSGL‐1 through ERM proteins

High expression of co-stimulatory and adhesion molecules are observed on eosinophils during human Schistosoma mansoni infection

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