Apoptotic-cell-derived membrane microparticles and IFN-α induce an inflammatory immune response.

A dysregulation in the clearance of apoptotic material is considered a major pathogenetic factor for the emergence of autoimmune diseases. Apoptotic-cell-derived membrane microparticles (AdMPs), which are released from the cell surface during apoptosis, have been implicated in the pathogenesis of autoimmunity. Also of importance are cytokines, such as interferon-α (IFN-α), which is known to be a major player in patients with systemic lupus erythematosus (SLE).

During apoptosis HMGB1 is translocated into apoptotic cell-derived membranous vesicles.

High mobility group box protein B1 (HMGB1), a nuclear protein reportedly involved in the structural organisation of DNA, is released from necrotic cells or upon cellular activation. After its release into the extracellular space, HMGB1 serves as a mediator of inflammation. In contrast to necrotic cells, apoptotic ones usually do not release HMGB1.

Apoptotic-cell-derived membrane vesicles induce an alternative maturation of human dendritic cells which is disturbed in SLE.

The clearance of apoptotic cells occurs in a non-inflammatory context. Defects in this clearance process have been linked to the emergence of human autoimmune diseases like systemic lupus erythematosus (SLE). A characteristic of apoptotic cell death is the shedding of membrane coated vesicles from the cellular surfaces.

Induction of type I IFN is a physiological immune reaction to apoptotic cell-derived membrane microparticles.

Membrane microparticles (MMP) released from apoptotic cells deliver signals that secure the anti-inflammatory response beyond the nearest proximity of the apoptotic cell. Plasmacytoid dendritic cells (pDC) are sentinels prepared to detect cellular processes that endanger the organism. They play a key role in the regulation of both pro- and anti-inflammatory immune responses.

Decrease of sialic acid residues as an eat-me signal on the surface of apoptotic lymphocytes.

The silent clearance of apoptotic cells is essential for cellular homeostasis in multicellular organisms, and several mediators of apoptotic cell recognition have been identified. However, the distinct mechanisms involved are not fully deciphered yet. We analyzed alterations of the glycocalyx on the surfaces of apoptotic cells and its impact for engulfment.

Clinical manifestations but not cytokine profiles differentiate adult-onset Still's disease and sepsis.

Objective: To analyze clinical manifestations, serum ferritin, and serum cytokine levels in patients with adult-onset Still's disease (AOSD) or bacterial sepsis and to evaluate their potential use for differential diagnosis.

Methods: Twenty-two consecutive patients with the first flare of AOSD and 6 patients with an established diagnosis of AOSD under immunosuppressive therapy were compared with 14 patients with bacterial sepsis. Clinical manifestations were scored in a Pouchot AOSD activity score including elevated serum ferritin levels to obtain a modified Pouchot score.

Cells induced to undergo apo in the presence of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone stimulate Mo derived phagocytes to secrete proinflammatory cytokines.

In contrast to nec, the apo is not accompanied by local inflammation. The immunosuppressive effects of apo cells have been repeatedly reported and a dysregulation of apo is discussed to play a major role in the pathogenesis of autoimmune disorders. The intracellular executioners of apo are the cysteine-aspartic acid proteases, also known as caspases that cleave a variety of intracellular substrates and mediate the morphological changes observed during apo.

Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE.

Autoantibodies against double-stranded DNA (dsDNA) and nucleosomes represent a hallmark of systemic lupus erythematosus (SLE). However, the mechanisms involved in breaking the immunological tolerance against these poorly immunogenic nuclear components are not fully understood. Impaired phagocytosis of apoptotic cells with consecutive release of nuclear antigens may contribute to the immune pathogenesis.

TLR9-activating DNA up-regulates ZAP70 via sustained PKB induction in IgM+ B cells.

In the past, ZAP70 was considered a T cell-specific kinase, and its aberrant expression in B-CLL cells was interpreted as a sign of malignant transformation and dedifferentiation. It was only recently that ZAP70 was detected in normal human B cells. In this study, we show that TLR9-activated B cells resemble B-cell chronic lymphocytic leukemia cells with regard to CD5, CD23, CD25, and heat shock protein 90 expression.

Hypothesis: human serum-borne albumin bound lipids promote cellular survival after apoptosis induction by a variety of stimuli.

A tight control of proliferation and cell death is required to maintain homeostasis in multicellular organisms. Several specific pro- and anti-apoptotic regulators and pathways have been deciphered being responsible for these complex tasks. Here we describe a human serum-borne activity promoting cellular fitness and inhibiting apoptosis after a plethora of different cell death stimuli.

The CFSE distribution assay is a powerful technique for the analysis of radiation-induced cell death and survival on a single-cell level.

Background And Purpose: To analyze radiation sensitivity of cells and to monitor cellular responses to irradiation, sensitive test systems for cell death and proliferation on a single-cell level are required. Traditionally, cellular radiation survival is measured using the clonogenic assay as the gold standard. Here it is reported, that labeling of cells with 5-(and 6-)carboxyfluorescein diacetate succinimidyl ester (CFDASE) can be used as a highly sensitive assay to determine cellular response toward irradiation on a single-cell level.

Loss of GM1 surface expression precedes annexin V-phycoerythrin binding of neutrophils undergoing spontaneous apoptosis during in vitro aging.

Background: Apoptosis of neutrophil granulocytes is an important determinant of the resolution of inflammation. Apoptotic neutrophils undergo specific alterations in their receptor profiles. These alterations are likely to contribute to the characteristic functional silencing of the dying cells.

Cooperation between C1q and DNase I in the clearance of necrotic cell-derived chromatin.

Objective: The efficient uptake of dying cells by phagocytes is essential to the avoidance of chronic inflammation. Some human autoimmune responses are thought to be driven by autoantigens from apoptotic or necrotic cells. We analyzed the role of C1q and DNase I in the disposal of necrotic cell-derived chromatin because deficiencies in these serum factors predispose to the development of systemic autoimmune disorders, such as systemic lupus erythematosus.

Early detection of apoptosis by staining of acid-treated apoptotic cells with FITC-labeled lectin from Narcissus pseudonarcissus.

Background: Exposure of anionic phospholipids and modified carbohydrates are main parts of the apoptotic death program. Cells undergoing apoptosis can be identified by various methods, detecting surface changes or modifications of their organelles, respectively. We describe a method for the detection of early apoptosis by staining of cells with fluorescein isothiocyanate (FITC)-labeled lectin from Narcissus pseudonarcissus (NPn).

Exposure of anionic phospholipids serves as anti-inflammatory and immunosuppressive signal--implications for antiphospholipid syndrome and systemic lupus erythematosus.

In contrast to necrotic cells, the clearance of apoptotic ones usually is an anti-inflammatory process which elicits only a marginal immune response. During apoptosis phosphatidylserine (PS) is exposed on the outer leaflet of the cytoplasmic membrane and serves as target for the PS receptor of phagocytes. The latter is responsible for anti-inflammatory signalling and the induction of TGFbeta.