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Apoptotic Blebs (apoptotic + bleb)

Distribution by Scientific Domains
Medical Sciences85%

Selected Abstracts

Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin-17

ARTHRITIS & RHEUMATISM, Issue 8 2009
Justin H. Fransen
Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the formation of antinuclear autoantibodies. Increased apoptosis and reduced clearance of apoptotic material have been assigned a role in the pathogenesis of SLE, but the underlying mechanisms remain elusive. During apoptosis apoptotic blebs are formed in which autoantigens are clustered. The cellular remnants after blebbing are referred to as apoptotic cell bodies. We undertook this study to compare the effects of apoptotic blebs and apoptotic cell bodies on maturation of dendritic cells (DCs) and their T cell stimulatory capacity in a murine setting. Methods The uptake by DCs of apoptotic blebs and apoptotic cell bodies was analyzed by flow cytometry and confocal microscopy. DC maturation and DC-induced T cell activation were determined by measuring expression of costimulatory molecules using flow cytometry and by measuring production of cytokines using enzyme-linked immunosorbent assay. Results DCs internalized apoptotic blebs more efficiently than apoptotic cell bodies. Incubation of DCs with apoptotic blebs resulted in increased CD40 and CD86 expression and increased interleukin-6 (IL-6) and tumor necrosis factor , production, while apoptotic cell bodies had no stimulatory effects. Using chloroquine, apoptotic bleb,induced DC maturation was shown to be independent of Toll-like receptors 3, 7, and 9. Interestingly, in cocultures with allogeneic T cells, bleb-matured DCs induced production of IL-2, interferon-,, and, in particular, IL-17, suggesting a Th1/Th17 response. Conclusion Apoptotic blebs, in contrast to apoptotic cell bodies, induce DC maturation, thereby providing DCs with increased Th17 cell stimulatory capacity. These data imply that apoptotic bleb,induced DC maturation represents an important driving force in the autoimmune response in SLE. [source]

Photosensitivity in lupus erythematosus

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2004
Noah Scheinfeld
Background: Lupus erythematosus is a systemic disease process that may manifest with a variety of internal and cutaneous findings. Photosensitivity is one the most common manifestations of lupus erythematosus. In patients with lupus erythematosus, there is a relationship between exposure to ultraviolet light, autoantibodies, genetics and other factors in the development of photosensitivity. Methods: Literature was reviewed on the topics of lupus erythematosus and photosensitivity discussed together and separately. The suggested mechanisms for their relationship were reviewed and analyzed. Results: Photosensitivity's relationship to and influence on the systemic manifestations of lupus remain to be defined. Mechanisms for photosensitivity might include: modulation of autoantibody location, cytotoxic effects, apoptosis induction with autoantigens in apoptotic blebs, upregulation of adhesion molecules and cytokines, induction of nitric oxide sythase expression and ultraviolet-generated antigenic DNA. Tumor necrosis factor , also seems to play a role in the development of photosensitivity. Conclusion: The basis for photosensitivity in lupus has yet to be fully defined. It is more commonly associated with subacute and tumid lupus erythematosus than with other variants. Anti-Ro antibodies appear to relate to photosensitivity. Tumor necrosis factor , polymorphisms appear to be important in some variants of lupus with photosensitivity. There is no sin que non antibody or mutation of photosensitivity in lupus. In patients with lupus, more work needs to be done to define the mechanisms of photosensitivity. [source]

Quantitative proteome analysis of detergent-resistant membranes identifies the differential regulation of protein kinase C isoforms in apoptotic T cells

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 15 2010
Therese Solstad
Abstract Several lines of evidence suggest that detergent-resistant membranes (DRMs) (also known as lipid rafts and glycosphingolipid-enriched microdomains) may have a role in signaling pathways of apoptosis. Here, we developed a method that combines DRMs isolation and methanol/chloroform extraction with stable isotope labeling with amino acids in cell culture-based quantitative proteome analysis of DRMs from control and cisplatin-induced apoptotic Jurkat T cells. This approach enabled us to enrich proteins with a pivotal role in cell signaling of which several were found with increased or decreased amounts in DRMs upon induction of apoptosis. Specifically, we show that three isoforms of protein kinase C (PKC) are regulated differently upon apoptosis. Although PKC, which belongs to the group of conventional PKCs is highly up-regulated in DRMs, the levels of two novel PKCs, PKC, and PKC,, are significantly reduced. These alterations/differences in PKC regulation are verified by immunoblotting and confocal microscopy. In addition, a specific enrichment of PKC, in apoptotic blebs and buds is shown. Furthermore, we observe an increased expression of ecto-PKC, as a result of exposure to cisplatin using flow cytometry. Our results demonstrate that in-depth proteomic analysis of DRMs provides a tool to study differential localization and regulation of signaling molecules important in health and disease. [source]

Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin-17

ARTHRITIS & RHEUMATISM, Issue 8 2009
Justin H. Fransen
Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the formation of antinuclear autoantibodies. Increased apoptosis and reduced clearance of apoptotic material have been assigned a role in the pathogenesis of SLE, but the underlying mechanisms remain elusive. During apoptosis apoptotic blebs are formed in which autoantigens are clustered. The cellular remnants after blebbing are referred to as apoptotic cell bodies. We undertook this study to compare the effects of apoptotic blebs and apoptotic cell bodies on maturation of dendritic cells (DCs) and their T cell stimulatory capacity in a murine setting. Methods The uptake by DCs of apoptotic blebs and apoptotic cell bodies was analyzed by flow cytometry and confocal microscopy. DC maturation and DC-induced T cell activation were determined by measuring expression of costimulatory molecules using flow cytometry and by measuring production of cytokines using enzyme-linked immunosorbent assay. Results DCs internalized apoptotic blebs more efficiently than apoptotic cell bodies. Incubation of DCs with apoptotic blebs resulted in increased CD40 and CD86 expression and increased interleukin-6 (IL-6) and tumor necrosis factor , production, while apoptotic cell bodies had no stimulatory effects. Using chloroquine, apoptotic bleb,induced DC maturation was shown to be independent of Toll-like receptors 3, 7, and 9. Interestingly, in cocultures with allogeneic T cells, bleb-matured DCs induced production of IL-2, interferon-,, and, in particular, IL-17, suggesting a Th1/Th17 response. Conclusion Apoptotic blebs, in contrast to apoptotic cell bodies, induce DC maturation, thereby providing DCs with increased Th17 cell stimulatory capacity. These data imply that apoptotic bleb,induced DC maturation represents an important driving force in the autoimmune response in SLE. [source]