Le CD154 plaquettaire : Une nouvelle interface dans l’hémostase et la réaction inflammatoire

Delmas, Yahsou; Viallard, Jean‐François; Villeneuve, Julien; Grosset, Christophe; Pasquet, Jean‐Max; Déchanet‐Merville, Julie; Nurden, Paquita; Pellegrin, Jean‐Luc; Rosenbaum, Jean; Combe, Christian; Ripoche, Jean

doi:10.1051/medsci/20052110825

Cited by 5 publications

(5 citation statements)

References 45 publications

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“…For example, platelets express all three receptors for sCD40L that have been identified to date (CD40, ␣5␤1, and ␣IIb␤3). Platelets are also the major source of circulating sCD40L (1) and, through their cell surface expression and release of CD40L, can play an important role in the immune response (62) and in inflammation (63). The roles played by each of three sCD40L receptors in platelet activation remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

CD40 Ligand Binds to α5β1 Integrin and Triggers Cell Signaling

Léveillé

Bouillon

Wen

et al. 2007

Journal of Biological Chemistry

110

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It was originally thought that the critical role of the CD40 ligand (CD40L) in normal and inflammatory immune responses was mainly mediated through its interaction with the classic receptor, CD40. However, data from CD40L ؊/؊ and CD40؊/؊ mice suggest that the CD40L-induced inflammatory immune response involves at least one other receptor. This hypothesis is supported by the fact that CD40L stabilizes arterial thrombi through an ␣IIb␤3-dependent mechanism. Here we provide evidence that soluble CD40L (sCD40L) binds to cells of the undifferentiated human monocytic U937 cell line in a CD40-and ␣IIb␤3-independent manner. Binding of sCD40L to U937 cells was inhibited by anti-CD40L monoclonal antibody 5C8, anti-␣5␤1 monoclonal antibody P1D6, and soluble ␣5␤1. The direct binding of sCD40L to purified ␣5␤1 was confirmed in a solid phase binding assay. Binding of sCD40L to ␣5␤1 was modulated by the form of ␣5␤1 expressed on the cell surface as the activation of ␣5␤1 by Mn 2؉ or dithiothreitol resulted in the loss of sCD40L binding. Moreover, sCD40L induced the translocation of ␣5␤1 to the Triton X-100-insoluble fraction of U937 cells, the rapid activation of the MAPK pathways ERK1/2, and interleukin-8 gene expression. The binding of sCD40L to CD40 on BJAB cells, an ␣5␤1-negative B cell line, and the resulting activation of ERK1/2 was not inhibited by soluble ␣5␤1, suggesting that sCD40L can bind concomitantly to both receptors. These results document the existence of novel CD40L-dependent pathways of physiological relevance for cells expressing multiple receptors (CD40, ␣5␤1, and ␣IIb␤3) for CD40L. (2). The expression of CD154 is inducible, and its expression on T cells is triggered primarily by T cell receptor signaling and is regulated by CD28-dependent and independent pathways (3) CD40L is stored in platelets and a subpopulation of T cells and rapidly translocates to the cell membrane following T cell and platelet activation (4, 5). A soluble form of biologically active CD40L trimer (sCD40L) is present in the supernatant of activated T cells (6) and platelets (7) and results from the proteolytic cleavage of the homotrimeric CD40L by a metalloproteinase (7).It was originally thought that CD40L had only one receptor, CD40, which is a type I transmembrane protein that is a member of the TNF receptor superfamily. CD40 is expressed on the surface of many immune and non-immune cells, including B lymphocytes, monocytes/macrophages, and dendritic cells, as well as platelets, epithelial, and endothelial cells (8). Most biological functions of CD40L have been attributed to its direct interaction with CD40. However, studies using CD40L Ϫ/Ϫ and CD40 Ϫ/Ϫ mice have suggested that CD40L may also bind to one or more other receptors (9). In support of this hypothesis, it has been elegantly demonstrated that sCD40L interacts with ␣IIb␤3 (GPIIb/IIIa), an integrin expressed on platelets (10), triggering outside-in signaling and inducing platelet activation and spreading (11). CD40L Ϫ/Ϫ mice exhibit increased bleeding time (12) and reduce...

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Section: Discussionmentioning

confidence: 99%

CD40 Ligand Binds to α5β1 Integrin and Triggers Cell Signaling

Léveillé

Bouillon

Wen

et al. 2007

Journal of Biological Chemistry

110

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“…Concurrently, allergens directly trigger platelet activation, leading to an upregulation of CD154 expression on platelets, a component involved in various immune responses, thereby facilitating the advancement of allergic asthma. This platelet activation is intricately linked to asthma exacerbation ( 33 , 34 ). Moreover, our research indicates that an escalation in SII potentially enhances the vigor of inflammatory cells within the airways, precipitating airway hyperresponsiveness and structural alterations, such as smooth muscle proliferation and submucosal fibrosis, which aggravate asthma symptoms and elevate the risk of its persistence ( 35 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

Association of systemic immune-inflammation index with asthma and asthma-related events: a cross-sectional NHANES-based study

Tian,

Xie,

Sun

2024

Front. Med.

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BackgroundAsthma is associated with persistent airway inflammation, and numerous studies have investigated inflammatory markers causing asthma. However, the systemic immune-inflammation index (SII) is a novel inflammatory marker, with scarce research reporting on the correlation between SII and asthma and asthma-related events.ObjectiveThe purpose of this study was to assess the relationship between SII and asthma and asthma-related events (including whether asthma is still present, asthma flare-ups in the past year, and asthma duration) using data from the National Health and Nutrition Examination Survey (NHANES).MethodsThe study utilized data from NHANES 2009–2018 with asthma and asthma-related events as dependent variables and SII as an independent variable. Multifactor logistic regression was employed to assess the correlation between the independent and dependent variables. Smoothed curve-fitting and threshold effect analyses were also carried out to determine the presence of non-linear relationships. Subgroup analyses were then performed to identify sensitive populations.ResultsIn this study, we analyzed data from 40,664 participants to elucidate the association between SII and asthma and its related events. The study findings indicated a positive correlation between SII and asthma, with a relative risk increase of 0.03% for asthma incidence per one percentage point increase in SII (OR = 1.0003, 95% CI: 1.0002, 1.0004). For individuals still suffering from asthma, higher SII also indicated a positive correlation with ongoing asthma (OR = 1.0004, 95% CI: 1.0001, 1.0006). However, no statistically significant association was observed between SII and asthma exacerbations within the following year (OR = 1.0001, p > 0.05). When considering the duration of asthma, we observed a slight positive correlation with SII (β = 0.0017, 95% CI: 0.0005, 0.0029). Additionally, a significant non-linear relationship between SII and asthma duration emerged at the threshold of 504.3 (β = 0.0031, 95% CI: 0.0014–0.0048, p = 0.0003). Subgroup analysis revealed a stronger correlation between SII and asthma in male patients (OR = 1.0004, 95% CI: 1.0002–1.0006) and individuals aged 60 and above (OR = 1.0005, 95% CI: 1.0003–1.0007). No gender differences were observed for individuals still suffering from asthma. However, the positive correlation between SII and asthma was more pronounced in participants under 20 years old (OR = 1.0004 in Model 3, 95% CI: 1.0002–1.0006). Specific sensitive subgroups for asthma exacerbation recurrence within the past year were not identified. When considering asthma duration, we observed this association to be significant in male individuals (β = 0.0031 in Model 3, 95% CI: 0.0014–0.0049) as well as individuals aged 20 to 39 (β = 0.0023 in Model 3, 95% CI: 0.0005–0.0040).ConclusionOur study concludes that SII is positively correlated with the persistence of asthma yet has limited predictive power for asthma recurrence. This highlights SII’s potential as a tool for assessing asthma risk and formulating targeted management strategies.

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“…This suggests that regulation of EGR-1 activity is an additional target for modulating platelet-mediated inflammatory activity. In addition to possible therapeutic significance, recent studies reveal that CD40L-dependent inflammatory activity of platelets is enhanced in several chronic inflammatory disease states, such as systemic lupus erythematosus and atherosclerosis, and that the enhanced inflammatory activity of platelets may contribute significantly to secondary pathology associated with progression of these diseases, including glomerulonephritis, plaque rupture, and increased thrombotic risk (4,7,44,45). Recent studies have established a relationship between rheumatoid arthritis and pathologic thrombopoiesis via systemic inflammatory and synovial growth factors feeding back into the bone marrow (46,47).…”

Section: Discussionmentioning

confidence: 99%

“…CD40L/CD40 interaction is required for enhancing antigenpresenting functions of dendritic cells, macrophages, and B cells; maturation of humoral responses; and enhancement of effector T cell responses (1). Additional functions of CD40L include the initiation of inflammatory and procoagulatory responses in vascular endothelial cells (2)(3)(4)(5). The emerging role of CD40L in immunity-associated inflammation implicates CD40L as a key player in cardiovascular disease and several chronic autoimmune inflammatory diseases that target the vasculature, including systemic lupus erythematosus, diabetes, and chronic kidney disease (6 -12).…”

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confidence: 99%

Early Growth Response-1 (EGR-1) and Nuclear Factor of Activated T Cells (NFAT) Cooperate to Mediate CD40L Expression in Megakaryocytes and Platelets

Crist

Elzey

Ahmann

et al. 2013

Journal of Biological Chemistry

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Background: Platelets mediate inflammatory activity through release of CD40L. Results: CD40L expression in platelets is regulated by NFATc2 and EGR-1 activation in megakaryocytes. Conclusion: Platelet inflammatory activity is dynamically regulated by exogenous factors that control NFAT and EGR-1 activity in megakaryocytes. Significance: The NFAT/EGR-1 axis in megakaryocytes may be a new target for treatment of chronic inflammatory diseases.

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Le CD154 plaquettaire : Une nouvelle interface dans l’hémostase et la réaction inflammatoire

Cited by 5 publications

References 45 publications

CD40 Ligand Binds to α5β1 Integrin and Triggers Cell Signaling

CD40 Ligand Binds to α5β1 Integrin and Triggers Cell Signaling

Association of systemic immune-inflammation index with asthma and asthma-related events: a cross-sectional NHANES-based study

Early Growth Response-1 (EGR-1) and Nuclear Factor of Activated T Cells (NFAT) Cooperate to Mediate CD40L Expression in Megakaryocytes and Platelets

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