Immune regulation by CD40-CD40-L interactions - 2; Y2K update

Kooten, Cees van

doi:10.2741/kooten

Cited by 53 publications

(32 citation statements)

References 162 publications

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“…The CD40 ligand (CD40L) is a transmembrane protein structurally related to tumor necrosis factor-␣ that has been first identified on CD4ϩ T cells (1,2). Subsequently, CD40L has been identified on the surface membrane of activated platelets (3) from where a soluble form of CD40L (sCD40L) can be released into the circulation (4).…”

Section: Introductionmentioning

confidence: 99%

Soluble CD40 Ligand Plasma Levels in Lung Cancer

Roselli¹,

Mineo

Basili³

et al. 2004

Clinical Cancer Research

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Purpose: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation.Experimental Design: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age-and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 ؉ 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples.Results: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 ؉ 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P ‫؍‬ 0.011) was independently related to sCD40L.Conclusions: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation.

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Section: Introductionmentioning

confidence: 99%

Soluble CD40 Ligand Plasma Levels in Lung Cancer

Roselli¹,

Mineo

Basili³

et al. 2004

Clinical Cancer Research

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“…[1][2][3] Beyond its function in cellmediated and humoral immunity, 4 ligation of CD40 on vascular cells, eg, endothelial cells (ECs), smooth muscle cells (SMCs), and monocytes/macrophages (M⌽), induces the expression of a variety of mediators implicated in atherogenesis, including adhesion molecules, chemokines, cytokines, growth factors, matrix-degrading enzymes, coagulation factors, and others (eg, cyclooxygenase-2, caspase-1, serine proteinase inhibitor-9). 1,5,6 In human as well as murine atherosclerotic lesions, the endothelium, SMC, M⌽, and T cells express CD40L and its receptor CD40.…”

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confidence: 99%

Atherogenesis in Mice Does Not Require CD40 Ligand From Bone Marrow–Derived Cells

Bavendiek

Zirlik

LaClair

et al. 2005

ATVB

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Objective-Recent research suggests a central role for CD40 ligand (CD40L) in atherogenesis. However, the relevant cellular source of this proinflammatory cytokine remains unknown. To test the hypothesis that CD40L expressed on hematopoietic cell types (eg, macrophages, lymphocytes, platelets) is crucial to atherogenesis, we performed bone marrow reconstitution experiments using low-density receptor-deficient (ldlr Ϫ/Ϫ ) and ldlr Ϫ/Ϫ /cd40l Ϫ/Ϫ compound-mutant mice. Methods and Results-As expected, systemic lack of CD40L in hypercholesterolemic ldlr Ϫ/Ϫ mice significantly reduced the development of atherosclerotic lesions in the aortic arch, aortic root, and abdominal aorta compared with ldlr

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“…Its interaction with CD40L, expressed on the surface of activated T cells, is essential for the generation of both humoral and cell-mediated immune responses. 1 The significance of CD40 to modulation of the immune system is clearly illustrated in individuals with the X-linked hyper IgM syndrome who are severely immunocompromised because of a mutational defect in the CD40L gene. 2 A growing body of literature now suggests that CD40/ CD40L interactions exert a wide range of biological effects across many cell types including monocytic cells, fibroblasts, endothelial cells, and malignant and normal epithelial cells.…”

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confidence: 99%

“…2 A growing body of literature now suggests that CD40/ CD40L interactions exert a wide range of biological effects across many cell types including monocytic cells, fibroblasts, endothelial cells, and malignant and normal epithelial cells. 1,3,4 CD40/CD40L interactions may play a central role not only in modulation of the immune system but also in that of the broader inflammatory response. The TNF ligands including CD40L (CD154) are generally highly specific for their cognate receptors, and it is thought that the pattern and intensity of intracellular signaling determines the downstream functional consequences of CD40/CD40L interaction.…”

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confidence: 99%

“…5 The consequences of CD40/CD40L interaction thus may include proliferation, survival, maturation, and cell death via apoptosis as well as alteration of expression of many inflammatory mediators including cytokines, chemokines, and adhesion molecules. 1,4,6 It is against this background that perturbation of the CD40/ CD40L pathway is seen as an attractive therapeutic target for autoimmune conditions such as systemic lupus erythematosis, allograft rejection, and also for chronic inflammatory conditions. [7][8][9] Although some studies have given encouraging indications of sustained long-term effects after single administrations of CD40L based gene therapy, the pathophysiologic significance of the highly diverse functional effects that may follow CD40/CD40L interaction remain unknown.…”

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confidence: 99%

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