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K Mahnke

Publications and source records attributed to K Mahnke.

25 records · Page 2Linked to original sources
PubMed1996

Interaction of murine dendritic cells with collagen up-regulates allostimulatory capacity, surface expression of heat stable antigen, and release of cytokines.

In vivo, dendritic cells (DC) reside in direct proximity to extracellular matrix (ECM) proteins. Because ECM proteins affect morphology and function of a number of cell types, this study investigated potential effects of ECM proteins on functional properties of DC. DC were generated from murine bone marrow cultures, supplemented with granulocyte-macrophage colony-stimulating factor, and subsequently cultured on tissue culture plates coated with various ECM proteins. Among the ECM proteins tested, collagen (COL) up-regulated the T cell stimulatory capacity of DC. This effect was accompanied by sustained surface expression of the co-stimulatory molecule heat stable antigen on DC and by enhanced release of interleukin-1 and interleukin-6, respectively. Because fibronectin or solubilized COL were unable to cause similar changes in DC phenotype or function, we conclude that adherence to COL interferes specifically with DC function. These data suggest that ECM proteins may be involved in regulation of DC phenotype as well as in their functional activation.

Animals↗
PubMed1995

Heterodimers of the calcium-binding proteins MRP8 and MRP14 are expressed on the surface of human monocytes upon adherence to fibronectin and collagen. Relation to TNF-alpha, IL-6, and superoxide production.

The 27E10 antigen is a heterodimer of MRP8 and MRP14, two Ca(2+)-binding proteins related to the S-100 protein family. Previous studies have shown that 27E10 epitope-bearing monocyte subsets are prevalent in early acute but absent in chronic inflammatory conditions. These observations further provide an impetus for identifying the cellular mechanisms responsible for the appearance of different monocyte subpopulations during inflammation. Therefore this in vitro study was carried out to investigate the influence of adhesion in inducing 27E10-positive subsets. In adhesion assays the role of 27E10 antigen in spontaneous adherence was obvious, as a monoclonal antibody directed against the 27E10 antigen significantly inhibited the adherence of monocytes to collagen and fibronectin. In contrast, these extracellular matrix (ECM) proteins induce the cell surface expression and association of 27E10 antigen with cytoskeleton (CSK), detected by flow cytometry and confocal laser scan microscopy, respectively. Similar results were obtained on cross-linking with specific antibodies, thus showing involvement of the integrin molecules VLA-2 and VLA-4. In addition, the association with CSK could be confirmed by differential detergent extraction. The observed redistribution of 27E10 antigen guided by collagen compared with fibronectin was also paralleled by an augmented release of inflammatory cytokines interleukin-6, tumor necrosis factor alpha, and superoxide anions. Thus, this study demonstrates that under inflammatory conditions the interactions of extravasating monocytes with the ECM may induce an activated phenotype of monocytes marked by 27E10.

Antigens↗
PubMed1995

Ultraviolet-B-induced apoptosis of keratinocytes: evidence for partial involvement of tumor necrosis factor-alpha in the formation of sunburn cells.

Irradiation with ultraviolet (UV) B radiation results in the formation of apoptotic keratinocytes called sunburn cells. Recently, it was demonstrated that keratinocytes can release tumor necrosis factor-alpha (TNF-alpha), which is known to cause apoptosis in particular cells. In addition, it has been shown that UVB light induces the release of TNF-alpha by keratinocytes and that keratinocytes express the 55-kD receptor for TNF-alpha. Therefore, we investigated whether TNF-alpha is involved in UV-induced apoptosis of keratinocytes. Normal human keratinocytes and HaCaT cells were exposed to UVB light, and apoptosis was examined by nick translation evaluated by fluorescence-activated cell sorter analysis. UVB induced apoptosis in a dose-dependent manner, which was confirmed by electron microscopy. Addition of a polyclonal antibody directed against human TNF-alpha immediately after UVB exposure was able to reduce DNA fragmentation. However, it was not possible to rescue all cells from apoptosis. To prove whether TNF-alpha is also involved in vivo in UVB-induced apoptosis of keratinocytes, Balb/c mice were exposed to UVB on their abdomens, skin biopsies were performed 24 h later, and sunburn cells were counted. A single dose of 2000 J/m2 caused a significant induction of sunburn cells. Subcutaneous injection of a polyclonal antibody directed against murine TNF-alpha immediately after UVB treatment resulted in a significant but incomplete reduction of sunburn cells, whereas injection of a rabbit IgG as a control had no effect. In both the in vitro and in vivo systems, application of recombinant TNF-alpha alone either to untreated keratinocytes or into normal murine skin did not induce sunburn cells. Thus, these data demonstrate that TNF-alpha is involved in UVB-induced apoptosis, but by itself is not able to induce sunburn cells. This further supports the notion that UVB-induced apoptosis of keratinocytes is a multifactorial event.

Animals↗
PubMed1994

Suppression of human mononuclear cell response by Helicobacter pylori: effects on isolated monocytes and lymphocytes.

Helicobacter pylori colonization of the human gastric mucosa causes a long-term, not self-limiting inflammation, suggesting that the microbe has properties to protect itself against the host immune defence system. Recently we were able to demonstrate that H. pylori suppresses the in vitro proliferative response of human peripheral blood mononuclear cells to antigens as well as to mitogens without affecting cell viability. The purpose of this study was to clarify which cell subsets of mononuclear cells are influenced by H. pylori. The use of monocytes which had been pretreated with a soluble cytoplasmic fraction of H. pylori (30 micrograms ml-1) led to a suppressed proliferation of T cells after PHA-activation. Activation of isolated T cells with PHA and PMA revealed that the proliferative response of lymphocytes could also be inhibited independently of monocytes. The anti-proliferative effect was associated with a reduction of IL-2 receptor (CD25) expression as well as an inhibition of blastogenesis. Furthermore, the spontaneous proliferation of EBV-transformed B cell lines was suppressed in a dose-dependent manner. FACS-analysis of HLA-DR, ICAM-1 and CD14 expression on the surface of monocytes revealed an influence of H. pylori on CD14 expression at a concentration of 30 micrograms ml-1, while the expression of HLA-DR and ICAM-1 was not affected at this concentration.

Antigens, CD↗
PubMed1992

The calcium-binding proteins MRP8 and MRP14 form a membrane-associated heterodimer in a subset of monocytes/macrophages present in acute but absent in chronic inflammatory lesions.

Monocytes/macrophages expressing an epitope recognized by a monoclonal antibody 27E10 are present in acute but are absent in chronic inflammatory disorders. This report shows that the 27E10 antigen is formed by noncovalent association of the two Ca(2+)-binding proteins MRP8 and MRP14 which belong to the S100 protein family. Identification has been confirmed immunochemically, by matrix-assisted UV-laser desorption/ionization spectrometry and by partial amino acid sequencing. Surface expression of the MRP8/MRP14 complex on a subset of monocytes is reported for the first time and shown to be up-regulated in a Ca(2+)-dependent manner. The 27E10 surface-positive monocytes isolated by cell separation techniques release high amounts of tumor necrosis factor-alpha and interleukin-1 beta in contrast to their 27E10 surface-negative counterparts thus emphasizing their role in inflammation.

Acute Disease↗
PubMedDate not supplied

A model to manage capitated risk.

The impact of increasing enrollment in Medicare HMOs will require health care providers to develop new strategies in care delivery systems. Key strategies in managing risk include health risk appraisals, proactive case management, disease management, provider education, and the use of inpatient physician managers. Implementing an integrated care management system requires a team approach. The physician inpatient manager, nurse case manager, geriatric clinical nurse specialist, and social worker composed the health care team charged with implementing a care management system responsive to enrollees' needs. A quality management plan is essential for tracking patient outcomes and quality indicators across the continuum. The focus of promoting wellness and preventing illness represents a paradigm shift from the traditional model of episodic care that can yield positive financial results.

Capitation Fee↗